Addressing the maturation of higher-order cognitive functions relevant to psychiatric disorders in mice

Psychiatric disorders are a large class of debilitating mental illnesses that affect everyday life of patients and people around them. In fact, they result in alteration of thinking, moods, behavior and increased risk of disability, pain, death, or loss of freedom. Nevertheless, the exact mechanisms behind these diseases are still unknown. Over the last few years, researchers focused on the study of abnormalities in brain neurodevelopment genetic mutations, impact of traumatic events and the interaction between these factors. In particular, both genetic and environmental factors may influence brain developmental process throughout childhood, adolescence and adulthood. Previous studies investigated how genetic and environmental risk factors act during sensitive brain developmental periods whereby altering adult behavior and possibly causing vulnerability to neuropsychiatric disorders. Different brain systems have been involved in the development of psychiatric disorders. However, for disorders such as attentional deficit hyperactivity disorder (ADHD), schizophrenia, and post-traumatic stress disorder (PTSD) there are consistent evidence of a major implication of the dopaminergic and endocannabinoid systems. Dopamine (DA) plays an important role acting as a trophic factor, in the development of neuronal cyto-architecture and also modulating neurodevelopmental processes during the embryonic and postnatal period. In particular, dopaminergic alterations within the prefrontal cortex (PFC) or Striatum, two brain area involved in cognition, learning and emotion, have been previously correlated to the etiology of neuropsychiatric disorders like schizophrenia, autism and ADHD. On the other hand, several studies have related dysfunctions of endocannabinoid system to psychiatric disorders. In fact, the relationship between cannabis consumption, especially during critical period of brain development, and schizophrenia onset has been demonstrated

Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

Systemic lipopolysaccharide (LPS) induces an acute inflammatory response in the central nervous system (CNS) (\u201cneuroinflammation\u201d) characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg) in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction

Addressing the maturation of higher-order cognitive functions relevant to psychiatric disorders in mice

Psychiatric disorders are a large class of debilitating mental illnesses that affect everyday life of patients and people around them. In fact, they result in alteration of thinking, moods, behavior and increased risk of disability, pain, death, or loss of freedom. Nevertheless, the exact mechanisms behind these diseases are still unknown. Over the last few years, researchers focused on the study of abnormalities in brain neurodevelopment genetic mutations, impact of traumatic events and the interaction between these factors. In particular, both genetic and environmental factors may influence brain developmental process throughout childhood, adolescence and adulthood. Previous studies investigated how genetic and environmental risk factors act during sensitive brain developmental periods whereby altering adult behavior and possibly causing vulnerability to neuropsychiatric disorders. Different brain systems have been involved in the development of psychiatric disorders. However, for disorders such as attentional deficit hyperactivity disorder (ADHD), schizophrenia, and post-traumatic stress disorder (PTSD) there are consistent evidence of a major implication of the dopaminergic and endocannabinoid systems. Dopamine (DA) plays an important role acting as a trophic factor, in the development of neuronal cyto-architecture and also modulating neurodevelopmental processes during the embryonic and postnatal period. In particular, dopaminergic alterations within the prefrontal cortex (PFC) or Striatum, two brain area involved in cognition, learning and emotion, have been previously correlated to the etiology of neuropsychiatric disorders like schizophrenia, autism and ADHD. On the other hand, several studies have related dysfunctions of endocannabinoid system to psychiatric disorders. In fact, the relationship between cannabis consumption, especially during critical period of brain development, and schizophrenia onset has been demonstrated

Effetti comportamentali della concomitante riduzione genica di DAT e COMT in un modello murino

Il disturbo da deficit dell'attenzione e dell'iperattività (ADHD) è un disordine dello sviluppo neuronale associato ad una serie di anomalie strutturali e funzionali del SNC. L'ADHD si manifesta in età infantile, ma persiste durante adolescenza ed età adulta. I potenziali fattori di rischio che predispongono al disturbo vengono detti fattori genetici e ambientali; l'ADHD è associato ad una disfunzione dopaminergica. Studi precedenti hanno preso in considerazione questo sistema sia perchè coinvolto nei processi cognitivi primari dell'attenzione e motori, sia perchè i trattamenti farmacologici utilizzati hanno come target il DAT. DAT si occupa della ricaptazione delle DA dallo spazio extracellulare

Attentional Control in Adolescent Mice Assessed with a Modified Five Choice Serial Reaction Time Task

Abstract Adolescence is a critical period for the development of higher-order cognitive functions. Unlike in humans, very limited tools are available to assess such cognitive abilities in adolescent rodents. We implemented a modified 5-Choice Serial Reaction Time Task (5CSRTT) to selectively measure attentiveness, impulsivity, broad monitoring, processing speed and distractibility in adolescent mice. 21-day old C57BL/6J mice reliably acquired this task with no sex-dependent differences in 10–12 days. A protocol previously used in adults was less effective to assess impulsiveness in adolescents, but revealed increased vulnerability in females. Next, we distinctively assessed selective, divided and broad monitoring attention modeling the human Spatial Attentional Resource Allocation Task (SARAT). Finally, we measured susceptibility to distractions using non-predictive cues that selectively disrupted attention. These paradigms were also applied to two genetically modified lines: the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT) heterozygous. Adolescent DAT hypo-functioning mice showed attentional deficits and higher impulsivity as found in adults. In contrast to adults, adolescent COMT hypo-functioning mice showed decreased impulsivity and attentional resilience to distractors. These paradigms open new avenues to study the establishment of higher-order cognitive functions in mice, as well as an effective tool for drug-testing and genetic screenings focused on adolescence

The Chance project: complex interventions with adolescent school drop-outs in Naples

In this paper the authors describe their long experience, as psychoanalytically oriented psychotherapists, with an experimental school project with adolescent school drop-outs, a project that has been running in three deprived contexts of Naples. In the paper the structure of the psychological project supporting workers involved with these disruptive adolescents is analysed in detail along with the theoretical framework that lies behind it. The authors also give some illustrations that show the intense dynamics present in this field of work and some meaningful developments observed in the relationships and communications between adolescents and adults and in the group of peers

Co-Ultramicronized Palmitoylethanolamide/Luteolin Facilitates the Development of Differentiating and Undifferentiated Rat Oligodendrocyte Progenitor Cells

Oligodendrocytes, the myelin-producing cells of the central nervous system (CNS), have limited capability to bring about repair in chronic CNS neuroinflammatory demyelinating disorders such as multiple sclerosis (MS). MS lesions are characterized by a compromised pool of undifferentiated oligodendrocyte progenitor cells (OPCs) unable to mature into myelin-producing oligodendrocytes. An attractive strategy may be to replace lost OLs and/or promote their maturation. N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide signaling molecule with anti-inflammatory and neuroprotective actions. Recent studies show a co-ultramicronized composite of PEA and the flavonoid luteolin (co-ultraPEALut) to be more efficacious than PEA in improving outcome in CNS injury models. Here, we examined the effects of co-ultraPEALut on development of OPCs from newborn rat cortex cultured under conditions favoring either differentiation (Sato medium) or proliferation (fibroblast growth factor-2 and platelet-derived growth factor (PDGF)-AA-supplemented serum-free medium (\u201cSFM\u201d)). OPCs in SFM displayed high expression of PDGF receptor alpha gene and the proliferation marker Ki-67. In Sato medium, in contrast, OPCs showed rapid decreases in PDGF receptor alpha and Ki-67 expression with a concomitant rise in myelin basic protein (MBP) expression. In these conditions, co-ultraPEALut (10 \u3bcM) enhanced OPC morphological complexity and expression of MBP and the transcription factor TCF7l2. Surprisingly, co-ultraPEALut also up-regulated MBP mRNA expression in OPCs in SFM. MBP expression in all cases was sensitive to inhibition of mammalian target of rapamycin. Within the context of strategies to promote endogenous remyelination in MS which focus on enhancing long-term survival of OPCs and stimulating their differentiation into remyelinating oligodendrocytes, co-ultraPEALut may represent a novel pharmacological approach