Adolescent \u3949-tetrahydrocannabinol exposure differently affects histone modifications in the brain of female and male rats

Despite the increasing evidence of a possible interaction between adolescent Cannabis abuse and the subsequent development of psychiatric disorders, Cannabis remains the illicit drug most abused by adolescents. We have previously demonstrated that female rats chronically treated during adolescence with increasing doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, develop a depressive/psychotic-like phenotype in adulthood. Interestingly, only chronic adolescent exposure to THC, but not adult exposure, led to this complex phenotype, suggesting that adolescence may represent a more vulnerable period for the adverse effect of THC. However, the neurobiology of this vulnerability is not still clear. Considering the important role assumed by epigenetics in the etiopathogenesis of psychiatric disorders, the main goal of this thesis is to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in other brain areas involved in the different aspects of the depressive/psychotic-like phenotype described in our animals. Specifically, we considered the Hippocampus for its involvement in cognition, the Nucleus Accumbens for its role in the reward circuit, and the Amygdala for its relevance in the emotional behaviour. To investigate the existence of age-specificity of THC effects, we performed the same analysis also after adult THC treatment. To investigate sex-dependency of THC response, we also checked THC response in adolescent male animals. First of all, adolescent (PND 35-45) and adult (PND 75-85) female Sprague-Dawley rats were treated twice a day with increasing intraperitoneal (ip) doses of THC: 2.5 mg/kg, 5 mg/kg, and 10 mg/kg or with its vehicle. Two, 24 and 48 hours after the end of the treatment, the brain areas of interest were collected and. Histone modifications associated with both transcriptional repression (H3K9 di- and tri-methylation, H3K27 trimethylation) and activation (H3K9 and H3K14 acetylation) were evaluated. Chronic THC exposure affected histone modifications in the brain of female rats in a region- and age-specific manner. Indeed, THC acted on different targets depending on the considered brain areas and, remarkably, the adolescent brain was generally more sensitive to THC exposure compared to the adult one. Specifically, in the Hippocampus of adolescent rats, THC induced a reduction of H3K14ac levels 2 hours after the end of the treatment. This was followed by a significant increase in di- and tri-methylation of H3K9 at 24 hours. Regarding the Nucleus Accumbens, H3K9me3 was significantly increased 2 hours after the end of the treatment. This enhancement was maintained 24 hours later, and it was paralleled by a significant increase in H3K9me2 and H3K14ac levels. On the contrary, at 48h, H3K9me3 levels, as well as H3K9me2 and H3K14ac levels were significantly reduced. In the Amygdala, THC administration induced a significant increase in H3K9me2 levels 2 hours after the end of the treatment. Twenty-four hours later, while this alteration returned to control values, H3K9me3 levels were significantly enhanced. Adult female rats exposed to chronic THC showed a different pattern of histone alterations. In the Hippocampus and Nucleus Accumbens, H3K14 acetylation levels were significantly increased, respectively, 2 and 24 hours after the end of the treatment. Intriguingly, a more complex picture is present in the adult Amygdala, in which a significant decrease in H3K9me2 and H3K27me3 were induced immediately after the cease of the treatment. Twenty-four hours later H3K9ac was significantly reduced, and at 48 hours, H3K14ac levels were significantly decreased. As a whole, the investigation performed in female rats suggests that in the adolescent brain THC induced a primary effect represented by changes leading to transcriptional repression, whereas the primary effect induced by adult THC exposure led to transcriptional activation. Interestingly, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to THC adverse effects. The second aim of this thesis was to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in different brain areas of male rats. To this aim, adolescent (PND 35-45) male Sprague-Dawley rats were treated with the same protocol previously described for females and we conducted the same analysis in the Prefrontal Cortex, Hippocampus and Nucleus Accumbens. Chronic THC exposure affected histone modifications in the brain of male rats in a region- specific manner. Surprisingly, in the Prefrontal cortex and Hippocampus, we did not found any histone alterations at any intervals of time, and only in the Nucleus Accumbens we found significant alterations in H3K9me3 levels. Specifically, H3K9me3 was decreased immediately after the end of the treatment and then increased 24h later. Further studies are needed to clarify the epigenetic landscape in the brain of male rats and how it could account for the development of the psychotic-like phenotype described in these animals. However, it is possible to conclude that Cannabis abuse during adolescence could impair the brain network functionality acting through a mechanism involving histone modifications that is characterized by sex-specificity

Adolescent Δ9-tetrahydrocannabinol exposure differently affects histone modifications in the brain of female and male rats

Despite the increasing evidence of a possible interaction between adolescent Cannabis abuse and the subsequent development of psychiatric disorders, Cannabis remains the illicit drug most abused by adolescents. We have previously demonstrated that female rats chronically treated during adolescence with increasing doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, develop a depressive/psychotic-like phenotype in adulthood. Interestingly, only chronic adolescent exposure to THC, but not adult exposure, led to this complex phenotype, suggesting that adolescence may represent a more vulnerable period for the adverse effect of THC. However, the neurobiology of this vulnerability is not still clear. Considering the important role assumed by epigenetics in the etiopathogenesis of psychiatric disorders, the main goal of this thesis is to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in other brain areas involved in the different aspects of the depressive/psychotic-like phenotype described in our animals. Specifically, we considered the Hippocampus for its involvement in cognition, the Nucleus Accumbens for its role in the reward circuit, and the Amygdala for its relevance in the emotional behaviour. To investigate the existence of age-specificity of THC effects, we performed the same analysis also after adult THC treatment. To investigate sex-dependency of THC response, we also checked THC response in adolescent male animals. First of all, adolescent (PND 35-45) and adult (PND 75-85) female Sprague-Dawley rats were treated twice a day with increasing intraperitoneal (ip) doses of THC: 2.5 mg/kg, 5 mg/kg, and 10 mg/kg or with its vehicle. Two, 24 and 48 hours after the end of the treatment, the brain areas of interest were collected and. Histone modifications associated with both transcriptional repression (H3K9 di- and tri-methylation, H3K27 trimethylation) and activation (H3K9 and H3K14 acetylation) were evaluated. Chronic THC exposure affected histone modifications in the brain of female rats in a region- and age-specific manner. Indeed, THC acted on different targets depending on the considered brain areas and, remarkably, the adolescent brain was generally more sensitive to THC exposure compared to the adult one. Specifically, in the Hippocampus of adolescent rats, THC induced a reduction of H3K14ac levels 2 hours after the end of the treatment. This was followed by a significant increase in di- and tri-methylation of H3K9 at 24 hours. Regarding the Nucleus Accumbens, H3K9me3 was significantly increased 2 hours after the end of the treatment. This enhancement was maintained 24 hours later, and it was paralleled by a significant increase in H3K9me2 and H3K14ac levels. On the contrary, at 48h, H3K9me3 levels, as well as H3K9me2 and H3K14ac levels were significantly reduced. In the Amygdala, THC administration induced a significant increase in H3K9me2 levels 2 hours after the end of the treatment. Twenty-four hours later, while this alteration returned to control values, H3K9me3 levels were significantly enhanced. Adult female rats exposed to chronic THC showed a different pattern of histone alterations. In the Hippocampus and Nucleus Accumbens, H3K14 acetylation levels were significantly increased, respectively, 2 and 24 hours after the end of the treatment. Intriguingly, a more complex picture is present in the adult Amygdala, in which a significant decrease in H3K9me2 and H3K27me3 were induced immediately after the cease of the treatment. Twenty-four hours later H3K9ac was significantly reduced, and at 48 hours, H3K14ac levels were significantly decreased. As a whole, the investigation performed in female rats suggests that in the adolescent brain THC induced a primary effect represented by changes leading to transcriptional repression, whereas the primary effect induced by adult THC exposure led to transcriptional activation. Interestingly, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to THC adverse effects. The second aim of this thesis was to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in different brain areas of male rats. To this aim, adolescent (PND 35-45) male Sprague-Dawley rats were treated with the same protocol previously described for females and we conducted the same analysis in the Prefrontal Cortex, Hippocampus and Nucleus Accumbens. Chronic THC exposure affected histone modifications in the brain of male rats in a region- specific manner. Surprisingly, in the Prefrontal cortex and Hippocampus, we did not found any histone alterations at any intervals of time, and only in the Nucleus Accumbens we found significant alterations in H3K9me3 levels. Specifically, H3K9me3 was decreased immediately after the end of the treatment and then increased 24h later. Further studies are needed to clarify the epigenetic landscape in the brain of male rats and how it could account for the development of the psychotic-like phenotype described in these animals. However, it is possible to conclude that Cannabis abuse during adolescence could impair the brain network functionality acting through a mechanism involving histone modifications that is characterized by sex-specificity

Prostorna raspodjela fizikalnih, kemijskih i bioloških oceanografskih karakteristika, fitoplanktona, hranjivih tvari i otopljene obojane organske materije (CDOM) u Bokokotorskom zaljevu na Jadranu

The temporal variations of temperature, salinity, fluorescence, dissolved oxygen concentration, Coloured Dissolved Organic Matter (CDOM) and of chemical (nutrients, chlorophyll a) and biological (phytoplankton composition) parameters in the Boka Kotorska Bay were observed during two periods. CDOM regulates the penetration of UV light into the sea and therefore plays an important role in many hydrological and biogeochemical processes in the sea surface layer including primary productivity. In the framework ADRICOSM-STAR it was possible to investigate the Boka Kotorska Bay during May and June 2008 in order to increase an understanding of optical and chemical characteristics and their evolution during these periods. In both periods station KO (located furthest from the open sea) presented different physical, chemical and biological characteristics with respect to the other stations inside the Boka Kotorska Bay. A positive correlation was found between CDOM and chlorophyll a (R = 0.7, P < 0.001, n = 15) and this implies that in this area, similarly to the open sea, the primary source of CDOM should be the biological production from phytoplankton. This is probably due to the fact that the rivers entering the Boka Kotorska Bay are not severely impacted by man.U Bokokotorskom zaljevu su mjerene vremenske promjene temperature, saliniteta, fluorescencije, koncentracije otopljenog kisika, obojene otopljene organske materije (CDOM) i kemijskih (hranjive soli, klorofila) i bioloških (sastav fitoplanktona) parametara tijekom dva razdoblja (svibanj i lipanj 2008. godine). CDOM određuje prodiranje UV svjetlosnih zraka u more i stoga igra vrlo važnu ulogu u mnogim hidrološkim i biogeokemijskim procesima u površinskom sloju mora koji uključuje primarnu produkciju. Unutar ADRICOSM-STAR projekta, bilo je moguće istražiti Bokokotorski zaljev tijekom svibnja i lipnja 2008. godine radi povećanja razumijevanja optičkih i kemijskih karakteristika i njihovog razvoja kroz ova razdoblja. Zbog dotoka krških rijeka i smanjenja razmjene s otvorenim morem, u oba razdoblja postaja KO (smještena najdalje od otvorenog mora) je pokazala različite fizikalne, kemijske i biolo{ke karakteristike u odnosu na postaje unutar Bokokotorskog zaljeva. Pronađena je pozitivna korelacija izme|u CDOM i klorofila a (R = 0.7, P < 0.001, n = 15) {to upućuje na to da bi u ovom području, slično otvorenom moru, primarni izvor CDOM trebao biti biološka produkcija od fitoplanktona. To je vjerojatno zbog toga što dotoci rijeka u Bokokotorskom zaljevu nisu ozbiljnije ugroženi ljudskim djelovanjem

&#945;-cyclodextrin and &#945;-cyclodextrin polymers as oxygen nanocarriers to limit hypoxia/reoxygenation injury: Implications from an in vitro model

The incidence of heart failure (HF) is increasing worldwide and myocardial infarction (MI), which follows ischemia and reperfusion (I/R), is often at the basis of HF development. Nanocarriers are interesting particles for their potential application in cardiovascular disease. Impaired drug delivery in ischemic disease is challenging. Cyclodextrin nanosponges (NS) can be considered innovative tools for improving oxygen delivery in a controlled manner. This study has developed new α-cyclodextrin-based formulations as oxygen nanocarriers such as native α-cyclodextrin (α-CD), branched α-cyclodextrin polymer (α-CD POLY), and α-cyclodextrin nanosponges (α-CD NS). The three different α-CD-based formulations were tested at 0.2, 2, and 20 µg/mL to ascertain their capability to reduce cell mortality during hypoxia and reoxygenation (H/R) in vitro protocols. H9c2, a cardiomyoblast cell line, was exposed to normoxia (20% oxygen) or hypoxia (5% CO2 and 95% N2). The different formulations, applied before hypoxia, induced a significant reduction in cell mortality (in a range of 15% to 30%) when compared to samples devoid of oxygen. Moreover, their application at the beginning of reoxygenation induced a considerable reduction in cell death (12% to 20%). α-CD NS showed a marked efficacy in controlled oxygenation, which suggests an interesting potential for future medical application of polymer systems for MI treatment

Assessment of spatio-temporal variability of faecal pollution along coastal waters during and after rainfall events

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Manini, E., Baldrighi, E., Ricci, F., Grilli, F., Giovannelli, D., Intoccia, M., Casabianca, S., Capellacci, S., Marinchel, N., Penna, P., Moro, F., Campanelli, A., Cordone, A., Correggia, M., Bastoni, D., Bolognini, L., Marini, M., & Penna, A. Assessment of spatio-temporal variability of faecal pollution along coastal waters during and after rainfall events. Water, 14(3), (2022): 502, https://doi.org/10.3390/w14030502.More than 80% of wastewaters are discharged into rivers or seas, with a negative impact on water quality along the coast due to the presence of potential pathogens of faecal origin. Escherichia coli and enterococci are important indicators to assess, monitor, and predict microbial water quality in natural ecosystems. During rainfall events, the amount of wastewater delivered to rivers and coastal systems is increased dramatically. This study implements measures capable of monitoring the pathways of wastewater discharge to rivers and the transport of faecal bacteria to the coastal area during and following extreme rainfall events. Spatio-temporal variability of faecal microorganisms and their relationship with environmental variables and sewage outflow in an area located in the western Adriatic coast (Fano, Italy) was monitored. The daily monitoring during the rainy events was carried out for two summer seasons, for a total of five sampling periods. These results highlight that faecal microbial contaminations were related to rainy events with a high flow of wastewater, with recovery times for the microbiological indicators varying between 24 and 72 h and influenced by a dynamic dispersion. The positive correlation between ammonium and faecal bacteria at the Arzilla River and the consequences in seawater can provide a theoretical basis for controlling ammonium levels in rivers as a proxy to monitor the potential risk of bathing waters pathogen pollution.This research was funded by WATERCARE project (Water management solutions for reducing microbial environment impact in coastal areas, project ID 10044130, https://www.italy-croatia.eu/web/watercare, accessed on 17 October 2021) funded by the European Union under the Interreg Italy–Croatia CBC Programme

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Adolescent Δ9-tetrahydrocannabinol exposure differently affects histone modifications in the brain of female and male rats

Despite the increasing evidence of a possible interaction between adolescent Cannabis abuse and the subsequent development of psychiatric disorders, Cannabis remains the illicit drug most abused by adolescents. We have previously demonstrated that female rats chronically treated during adolescence with increasing doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive ingredient of cannabis, develop a depressive/psychotic-like phenotype in adulthood. Interestingly, only chronic adolescent exposure to THC, but not adult exposure, led to this complex phenotype, suggesting that adolescence may represent a more vulnerable period for the adverse effect of THC. However, the neurobiology of this vulnerability is not still clear. Considering the important role assumed by epigenetics in the etiopathogenesis of psychiatric disorders, the main goal of this thesis is to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in other brain areas involved in the different aspects of the depressive/psychotic-like phenotype described in our animals. Specifically, we considered the Hippocampus for its involvement in cognition, the Nucleus Accumbens for its role in the reward circuit, and the Amygdala for its relevance in the emotional behaviour. To investigate the existence of age-specificity of THC effects, we performed the same analysis also after adult THC treatment. To investigate sex-dependency of THC response, we also checked THC response in adolescent male animals. First of all, adolescent (PND 35-45) and adult (PND 75-85) female Sprague-Dawley rats were treated twice a day with increasing intraperitoneal (ip) doses of THC: 2.5 mg/kg, 5 mg/kg, and 10 mg/kg or with its vehicle. Two, 24 and 48 hours after the end of the treatment, the brain areas of interest were collected and. Histone modifications associated with both transcriptional repression (H3K9 di- and tri-methylation, H3K27 trimethylation) and activation (H3K9 and H3K14 acetylation) were evaluated. Chronic THC exposure affected histone modifications in the brain of female rats in a region- and age-specific manner. Indeed, THC acted on different targets depending on the considered brain areas and, remarkably, the adolescent brain was generally more sensitive to THC exposure compared to the adult one. Specifically, in the Hippocampus of adolescent rats, THC induced a reduction of H3K14ac levels 2 hours after the end of the treatment. This was followed by a significant increase in di- and tri-methylation of H3K9 at 24 hours. Regarding the Nucleus Accumbens, H3K9me3 was significantly increased 2 hours after the end of the treatment. This enhancement was maintained 24 hours later, and it was paralleled by a significant increase in H3K9me2 and H3K14ac levels. On the contrary, at 48h, H3K9me3 levels, as well as H3K9me2 and H3K14ac levels were significantly reduced. In the Amygdala, THC administration induced a significant increase in H3K9me2 levels 2 hours after the end of the treatment. Twenty-four hours later, while this alteration returned to control values, H3K9me3 levels were significantly enhanced. Adult female rats exposed to chronic THC showed a different pattern of histone alterations. In the Hippocampus and Nucleus Accumbens, H3K14 acetylation levels were significantly increased, respectively, 2 and 24 hours after the end of the treatment. Intriguingly, a more complex picture is present in the adult Amygdala, in which a significant decrease in H3K9me2 and H3K27me3 were induced immediately after the cease of the treatment. Twenty-four hours later H3K9ac was significantly reduced, and at 48 hours, H3K14ac levels were significantly decreased. As a whole, the investigation performed in female rats suggests that in the adolescent brain THC induced a primary effect represented by changes leading to transcriptional repression, whereas the primary effect induced by adult THC exposure led to transcriptional activation. Interestingly, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to THC adverse effects. The second aim of this thesis was to extend our knowledge on the impact of adolescent THC exposure on histone modifications occurring in different brain areas of male rats. To this aim, adolescent (PND 35-45) male Sprague-Dawley rats were treated with the same protocol previously described for females and we conducted the same analysis in the Prefrontal Cortex, Hippocampus and Nucleus Accumbens. Chronic THC exposure affected histone modifications in the brain of male rats in a region- specific manner. Surprisingly, in the Prefrontal cortex and Hippocampus, we did not found any histone alterations at any intervals of time, and only in the Nucleus Accumbens we found significant alterations in H3K9me3 levels. Specifically, H3K9me3 was decreased immediately after the end of the treatment and then increased 24h later. Further studies are needed to clarify the epigenetic landscape in the brain of male rats and how it could account for the development of the psychotic-like phenotype described in these animals. However, it is possible to conclude that Cannabis abuse during adolescence could impair the brain network functionality acting through a mechanism involving histone modifications that is characterized by sex-specificity

PSYCHOLOGICAL WELL-BEING IN ITALIAN ELDERS WITH AND WITHOUT PARKINSON’S DISEASE: A PRELIMINARY STUDY

Chronic degenerative conditions characterized by motor dysfunction such as Parkinson’s disease may impact the determinants of quality of life in late adulthood, such as psychological well-being (PWB) and affective status. Nonetheless, this issue has not been substantially investigated in the Italian population. Here in a preliminary study we explored relationships between several mental health and motor functions in a group of 30 cognitively healthy community-dwelling Italian elderly with and without Parkinson’s disease (mean age = 74.3 years, SD = 7.1). Each participant was individually presented with a battery of psychological and motor tests assessing cognitive efficiency, PWB, affective status, lifestyle, handgrip strength, three-dimensional gait analysis, and static balance (through postural sway analysis). In particular, kinematics of gait was characterized by means of Gait Profile Score (GPS), a synthetic measure of the deviation of the gait from physiologic conditions. Statistically significant Pearson’s product-moment correlations were found between maximal handgrip strength and several PWB indexes. Moreover, patients with Parkinson’s disease reported lower perceived physical health and personal satisfaction, as well as increased values of GPS than controls, however greater depressive signs were not found in the former group. Finally, a linear regression analysis revealed that the occurrence of Parkinson’s disease explains 26% of the variance relative to a self-reported personal satisfaction index. These preliminary outcomes highlight a general link between motor and psychological outcomes and the impact of Parkinson’s disease on both

Variability of hydrographic and biogeochemical properties in the North-western Adriatic coastal waters in relation to river discharge and climate changes

The dynamics of hydrographic and biogeochemical properties in a Northwestern coastal area of the Adriatic Sea were investigated. The time series data from continuous observation (2007–2022) allowed the investigation of annual trends and seasonal cycles along a coastal transect influenced by local river discharge. Various statistical models were used to investigate water temperature, salinity, chlorophyll a, dissolved organic, inorganic and particulate nutrients, precipitation and river discharge. It was found that the local river discharge regime played an essential role in interannual, and seasonal biogeochemical dynamics associated with global climate change in the Mediterranean region. A significant trend towards oligotrophic conditions was detected, as evidenced by the downward trend in the river mouth and on the sea of chlorophyll a (−0.2 μg L−1 in the sea), dissolved organic and inorganic nitrogen and phosphorus (i.e., −0.43 μM yr−1 of DON in the sea and −6.67 of DIN μM yr−1 in the river mouth or −0.07 μM yr−1 of DOP and −0.02 μM yr−1 of DIP in the river mouth) and silicate (−2.47 μM yr−1 in the river mouth) concentrations. Salinity showed a long-term increase in the sea (0.08 yr−1), corresponding to a significant decrease in water discharge from the local river (−0.27 m3 s−1 yr−1) and precipitation (−0.06 mm yr−1). The dissolved organic and inorganic nutrients highlighted a different seasonal accumulation under the river runoff regime. The nutrient enrichment was predominantly driven by river contribution. Data analysis showed that the coastal biogeochemical properties dynamics were mostly influenced by river discharge and precipitation regimes, which in turn are driven by climate change variability in the North-western Adriatic Sea