Morphological changes in dopaminergic structures of the rat brain conditioned by maternal deprivation

Maternalna deprivacija (MD) predstavlja rano odvajanje mladunaca od majke i opšte prihvaćeni animalni model stresa. Rana traumatična iskustva tokom života izazivaju dugotrajne promene u mozgu koje mogu potrajati i kasnije u životu. Ove promene su sastavni deo etiologije psihijatrijskih poremećaja. Faktori kao što su stres i pothranjenost kod majke tokom fetalnog razvoja, se razmatraju kao dopunski faktori rizika u nastanku shizofrenije. Cilj ovog istraživanja je bio da se ispitaju dugotrajne morfološke promene u dopaminergičkim strukturama mozga adolescentnih i adultnih pacova nakon maternalne deprivacije. Materijal i metode : U eksperimentima su korišćeni pacovi muškog pola soja Wistar. Dan porođaja smo označili kao nulti postnatalni dan (PN 0). Devetog postnatalnog dana (PN 9) legla smo podvrgnuli 24-časovnoj maternalnoj deprivaciji. Životinje su žrtvovane trideset i petog (PN 35) i šezdesetog postnatalnog dana (PN 60) kako bi se ispitale dugotrajne posledice MD. Mikroskopske morfometrijske metode su korišćene za merenje volumena dopaminergičkih jedara, broja i gustine TH+ neurona u jedrima. Biohemijske metode su korišćene za određivanje koncentracije kortikosterona u krvi ispitivanih životinja. Volumen dopaminergičkih jedara i broj dopaminergičkih neurona u substantia-i nigra-i (SN), ventralnom tegmentalnom području (VTA) i locus coeruleus- u (LC) analizirani su u tri stereotaksičke koordinate u odnosu na kraniometrijsku tačku bregma. Rezultati : Ključni rezultati ovog istraživanja su da adolescentni i adultni mozak pacova podleže promenama u ispitivanim parametrima koje su prouzrokovane stresom u ranom životnom periodu, praćenim povišenjem nivoa kortikosterona u krvi. Takođe, MD je prouzrokovala gubitak telesne težine u juvenilnom, adolescentnom i adultnom periodu života. Konkretno, maternalna deprivacija povećava volumen svih dopaminergičkih jedara i ukupan broj dopaminergičkih neurona u njima u periodu adolescencije i odrasle dobi. Zaključak : Postnatalno odvajanje mladunaca od majke prouzrokovalo je nepravilan razvoj dopaminergičkog sistema, za koji se pretpostavlja da igra ulogu u patologiji psihijatrijskih bolesti. Ovo istraživanje korelira sa dopaminskom teorijom nastanka shizofrenije.Background : Maternal deprivation (MD) is the early separation of pups from the mother and generally accepted animal model of stress. Early traumatic experiences during life cause long-term changes in the brain that can last later in life. These changes are an integral part of the etiology of psychiatric disorders. Factors such as maternal stress and malnutrition during fetal development are considered as additional risk factors in the development of schizophrenia. The aim of this study was to examine long-term morphological changes in the dopaminergic brain structures of adolescent and adult rats after maternal deprivation. Material and Methods : Male Wistar rats were used in the experiments. We marked the day of delivery as zero postnatal day (PN 0). On the ninth postnatal day (PN 9), we subjected the litter to 24-hour maternal deprivation. Animals were sacrificed on the thirty-fifth (PN 35) and sixtieth postnatal day (PN 60) to investigate the long-term consequences of MD. Microscopic morphometric methods were used to measure the volume of dopaminergic nuclei, the number and density of TH + neurons in the nuclei. Biochemical methods were used to determine the concentration of corticosterone in the blood of the tested animals. The volume of dopaminergic nuclei and the number of dopaminergic neurons in the substantia nigra (SN), ventral tegmental region (VTA) and locus coeruleus (LC) were analyzed in three stereotaxic ranges relative to the craniometric point bregma. Results : The key results of this study are that the adolescent and adult brains of rats undergo changes in the examined parameters caused by stress in early life, followed by an increase in corticosterone levels in the blood. Also, MD caused weight loss in the juvenile, adolescent and adult periods of life. In particular, maternal deprivation increases the volume of all dopaminergic nuclei and the total number of dopaminergic neurons in them during adolescence and adulthood. Conclusion : Postnatal separation of pups from the mother caused an improper development of the dopaminergic system, which is assumed to play a role in the pathology of psychiatric diseases. This research correlates with the dopamine theory of schizophreni

Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat

Our previous studies in the rat model of Parkinson’s disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats

Alterations of Sleep and Sleep Oscillations in the Hemiparkinsonian Rat.

Our previous studies in the rat model of Parkinson's disease (PD) cholinopathy demonstrated the sleep-related alterations in electroencephalographic (EEG) oscillations at the cortical and hippocampal levels, cortical drives, and sleep spindles (SSs) as the earliest functional biomarkers preceding hypokinesia. Our aim in this study was to follow the impact of a unilateral substantia nigra pars compacta (SNpc) lesion in rat on the cortical and hippocampal sleep architectures and their EEG microstructures, as well as the cortico-hippocampal synchronizations of EEG oscillations, and the SS and high voltage sleep spindle (HVS) dynamics during NREM and REM sleep. We performed unilateral SNpc lesions using two different concentrations/volumes of 6-hydroxydopamine (6-OHDA; 12 μg/1 μl or 12 μg/2 μl). Whereas the unilateral dopaminergic neuronal loss >50% throughout the overall SNpc rostro-caudal dimension prolonged the Wake state, with no change in the NREM or REM duration, there was a long-lasting theta amplitude augmentation across all sleep states in the motor cortex (MCx), but also in the CA1 hippocampus (Hipp) during both Wake and REM sleep. We demonstrate that SS are the hallmarks of NREM sleep, but that they also occur during REM sleep in the MCx and Hipp of the control rats. Whereas SS are always longer in REM vs. NREM sleep in both structures, they are consistently slower in the Hipp. The dopaminergic neuronal loss increased the density of SS in both structures and shortened them in the MCx during NREM sleep, without changing the intrinsic frequency. Conversely, HVS are the hallmarks of REM sleep in the control rats, slower in the Hipp vs. MCx, and the dopaminergic neuronal loss increased their density in the MCx, but shortened them more consistently in the Hipp during REM sleep. In addition, there was an altered synchronization of the EEG oscillations between the MCx and Hipp in different sleep states, particularly the theta and sigma coherences during REM sleep. We provide novel evidence for the importance of the SNpc dopaminergic innervation in sleep regulation, theta rhythm generation, and SS/HVS dynamics control. We suggest the importance of the underlying REM sleep regulatory substrate to HVS generation and duration and to the cortico-hippocampal synchronizations of EEG oscillations in hemiparkinsonian rats

Anatomic and MRI bases for pontine infarctions with patients presentation

Objectives: There are scarce data regarding pontine arteries anatomy, which is the basis for ischemic lesions following their occlusion. The aim of this study was to examine pontine vasculature and its relationships with the radiologic and neuro-logic features of pontine infarctions. Materials and methods: Branches of eight basilar arteries and their twigs, including the larger intrapontine branches, were microdis-sected following an injection of a 10% mixture of India ink and gelatin. Two addi-tional brain stems were prepared for microscopic examination after being stained with luxol fast blue and cresyl violet. Finally, 30 patients with pontine infarctions underwent magnetic resonance imaging (MRI) in order to determine the position and size of the infarctions. Results: The perforating arteries, which averaged 5.8 in number and 0.39 mm in diameter, gave rise to paramedian and anteromedial branches, and also to anterolateral twigs (62.5%). The longer leptomeningeal and cere-bellar arteries occasionally gave off perforating and anterolateral twigs, and either the lateral or posterior branches. Occlusion of some of these vessels resulted in the para-median (30%), anterolateral (26.7%), lateral (20%), and combined infarctions (23.3%), which were most often isolated and unilateral, and rarely bilateral (10%). They were located in the lower pons (23.3%), middle (10%) or rostral (26.7%), or in two or three portions (40%). Each type of infarction usually produced characteristic neurologic signs. The clinical significance of the anatomic findings was discussed. Conclusions: There was a good correlation between the intrapontine vascular territories, the position, size and shape of the infarctions, and the type of neurologic manifestations. (c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Long-Term Effects of Maternal Deprivation on the Volume of Dopaminergic Nuclei and Number of Dopaminergic Neurons in Substantia Nigra and Ventral Tegmental Area in Rats

Early life adversities leave long-lasting structural and functional consequences on the brain, which may persist later in life. Dopamine is a neurotransmitter that is extremely important in mood and motor control. The aim of this study was to investigate the effect of maternal deprivation during the ninth postnatal day on the volume of dopaminergic nuclei and the number of dopaminergic neurons in adolescence and adulthood. Maternally deprived and control Wistar rats were sacrificed on postnatal day 35 or 60, and the dopaminergic neurons were stained in coronal histological sections of ventral midbrain with the tyrosine hydroxylase antibody. The volume of dopaminergic nuclei and the number of dopaminergic neurons in the substantia nigra (SN) and ventral tegmental area (VTA) were analyzed in three representative coordinates. Maternal deprivation caused weight loss on postnatal day 21 (weaning) and corticosterone blood level elevation on postnatal days 35 and 60 in stressed compared to control rats. In maternally deprived animals, the volumes of SN and VTA were increased compared to the controls. This increase was accompanied by an elevation in the number of dopaminergic neurons in both nuclei. Altogether, based on somatic and corticosterone level measurements, maternal deprivation represents a substantial adversity, and the phenotype it causes in adulthood includes increased volume of the dopaminergic nuclei and number of dopaminergic neurons

INTERNAL ENERGY OF HEISENBERG SPIN-1/2 J1 - J2 ANTIFERROMAGNET ON THE BODY-CENTERED-CUBIC LATTICE IN TYABLIKOV APPROXIMATION

Magnetic properties of spin ½ J1-J2 quantum Heisenberg antiferromagnet on body centered cubic lattice are investigated in the paper. By using two-time temperature Green's functions, sublattice magnetization and critical temperature depending on the frustration ratio J2/ J1 are obtained in both stripe and Neel phase. The analysis of ground state sublattice magnetization and internal energy indicates the first order phase transition from Neel to stripe phase for  0.7< J2/ J1< 0.8, which is in agreement with previous studies.Magnetic properties of spin ½ J1-J2 quantum Heisenberg antiferromagnet on body centered cubic lattice are investigated in the paper. By using two-time temperature Green's functions, sublattice magnetization and critical temperature depending on the frustration ratio J2/ J1 are obtained in both stripe and Neel phase. The analysis of ground state sublattice magnetization and internal energy indicates the first order phase transition from Neel to stripe phase for  0.7< J2/ J1< 0.8, which is in agreement with previous studies

Morphological changes in dopaminergic structures of the rat brain conditioned by maternal deprivation

Maternalna deprivacija (MD) predstavlja rano odvajanje mladunaca od majke i opšte prihvaćeni animalni model stresa. Rana traumatična iskustva tokom života izazivaju dugotrajne promene u mozgu koje mogu potrajati i kasnije u životu. Ove promene su sastavni deo etiologije psihijatrijskih poremećaja. Faktori kao što su stres i pothranjenost kod majke tokom fetalnog razvoja, se razmatraju kao dopunski faktori rizika u nastanku shizofrenije. Cilj ovog istraživanja je bio da se ispitaju dugotrajne morfološke promene u dopaminergičkim strukturama mozga adolescentnih i adultnih pacova nakon maternalne deprivacije. Materijal i metode : U eksperimentima su korišćeni pacovi muškog pola soja Wistar. Dan porođaja smo označili kao nulti postnatalni dan (PN 0). Devetog postnatalnog dana (PN 9) legla smo podvrgnuli 24-časovnoj maternalnoj deprivaciji. Životinje su žrtvovane trideset i petog (PN 35) i šezdesetog postnatalnog dana (PN 60) kako bi se ispitale dugotrajne posledice MD. Mikroskopske morfometrijske metode su korišćene za merenje volumena dopaminergičkih jedara, broja i gustine TH+ neurona u jedrima. Biohemijske metode su korišćene za određivanje koncentracije kortikosterona u krvi ispitivanih životinja. Volumen dopaminergičkih jedara i broj dopaminergičkih neurona u substantia-i nigra-i (SN), ventralnom tegmentalnom području (VTA) i locus coeruleus- u (LC) analizirani su u tri stereotaksičke koordinate u odnosu na kraniometrijsku tačku bregma. Rezultati : Ključni rezultati ovog istraživanja su da adolescentni i adultni mozak pacova podleže promenama u ispitivanim parametrima koje su prouzrokovane stresom u ranom životnom periodu, praćenim povišenjem nivoa kortikosterona u krvi. Takođe, MD je prouzrokovala gubitak telesne težine u juvenilnom, adolescentnom i adultnom periodu života. Konkretno, maternalna deprivacija povećava volumen svih dopaminergičkih jedara i ukupan broj dopaminergičkih neurona u njima u periodu adolescencije i odrasle dobi. Zaključak : Postnatalno odvajanje mladunaca od majke prouzrokovalo je nepravilan razvoj dopaminergičkog sistema, za koji se pretpostavlja da igra ulogu u patologiji psihijatrijskih bolesti. Ovo istraživanje korelira sa dopaminskom teorijom nastanka shizofrenije.Background : Maternal deprivation (MD) is the early separation of pups from the mother and generally accepted animal model of stress. Early traumatic experiences during life cause long-term changes in the brain that can last later in life. These changes are an integral part of the etiology of psychiatric disorders. Factors such as maternal stress and malnutrition during fetal development are considered as additional risk factors in the development of schizophrenia. The aim of this study was to examine long-term morphological changes in the dopaminergic brain structures of adolescent and adult rats after maternal deprivation. Material and Methods : Male Wistar rats were used in the experiments. We marked the day of delivery as zero postnatal day (PN 0). On the ninth postnatal day (PN 9), we subjected the litter to 24-hour maternal deprivation. Animals were sacrificed on the thirty-fifth (PN 35) and sixtieth postnatal day (PN 60) to investigate the long-term consequences of MD. Microscopic morphometric methods were used to measure the volume of dopaminergic nuclei, the number and density of TH + neurons in the nuclei. Biochemical methods were used to determine the concentration of corticosterone in the blood of the tested animals. The volume of dopaminergic nuclei and the number of dopaminergic neurons in the substantia nigra (SN), ventral tegmental region (VTA) and locus coeruleus (LC) were analyzed in three stereotaxic ranges relative to the craniometric point bregma. Results : The key results of this study are that the adolescent and adult brains of rats undergo changes in the examined parameters caused by stress in early life, followed by an increase in corticosterone levels in the blood. Also, MD caused weight loss in the juvenile, adolescent and adult periods of life. In particular, maternal deprivation increases the volume of all dopaminergic nuclei and the total number of dopaminergic neurons in them during adolescence and adulthood. Conclusion : Postnatal separation of pups from the mother caused an improper development of the dopaminergic system, which is assumed to play a role in the pathology of psychiatric diseases. This research correlates with the dopamine theory of schizophreni

Molecular Aspects of MAFLD—New Insights on Pathogenesis and Treatment

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications