Shank3 deficiency alters midbrain GABAergic neuron morphology, GABAergic markers and synaptic activity in primary striatal neurons.

Abnormalities in gamma-aminobutyric acid (GABA)ergic neurotransmission play a role in the pathogenesis of autism, although the mechanisms responsible for alterations in specific brain regions remain unclear. Deficits in social motivation and interactions are core symptoms of autism, likely due to defects in dopaminergic neural pathways. Therefore, investigating the morphology and functional roles of GABAergic neurons within dopaminergic projection areas could elucidate the underlying etiology of autism.

Developmental effects of oxytocin on GABAergic neurons in the olfactory brain regions.

Oxytocin affects social recognition, interactions, and behavior in adults. Despite growing data on the role of oxytocin in the sensory systems, its effects on early olfactory system development remain poorly understood. The present study aimed to investigate the developmental impact of oxytocin on selected parameters of the GABAergic system in olfactory brain regions.

Oxytocin, GABA, and dopamine interplay in autism.

Oxytocin plays an important role in brain development and is associated with various neurotransmitter systems in the brain. Abnormalities in the production, secretion, and distribution of oxytocin in the brain, at least during some stages of the development, are critical for the pathogenesis of neuropsychiatric diseases, particularly in the autism spectrum disorder. The etiology of autism includes changes in local sensory and dopaminergic areas of the brain, which are also supplied by the hypothalamic sources of oxytocin.

Shank3 Deficiency Results in a Reduction in GABAergic Postsynaptic Puncta in the Olfactory Brain Areas.

Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances in olfactory processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the olfactory system in ASD remains unclear.

Mini review of molecules involved in altered postnatal neurogenesis in autism.

The neurobiology of autism is complex, but emerging research points to potential abnormalities and alterations in neurogenesis. The aim of the present review is to describe the advances in the understanding of the role of selected neurotrophins, neuropeptides, and other compounds secreted by neuronal cells in the processes of postnatal neurogenesis in conjunction with autism. We characterize the fundamental mechanisms of neuronal cell proliferation, generation of major neuronal cell types with special emphasis on neurogenic niches - the subventricular zone and hippocampal areas.

Neonatal oxytocin treatment alters levels of precursor and mature BDNF forms and modifies the expression of neuronal markers in the male rat hippocampus.

Neuropeptide oxytocin appears to be involved in the formation of hippocampal circuitry, underlying social memory and behaviour. Recent studies point to the role of oxytocin in regulating the levels of nerve growth factors that could influence neurogenesis and neuritogenesis during the early stages of brain development. Therefore, the aim of the present study was to evaluate the early developmental effect of oxytocin administration (P2 and P3 days, two doses, 5 μg/pup, s.

Effects of antipsychotics, haloperidol and olanzapine, on the expression of apoptosis-related genes in mouse mHippoE-2 cells and rat hippocampus.

Modified levels of pro- (caspase3, Bax) and anti-apoptotic (Bcl-2) regulatory proteins have been detected in certain brain areas of schizophrenic patients indicating a possible dysregulation of apoptosis. In the present study, effects of antipsychotics, haloperidol (HAL) and olanzapine (OLA), on the gene expression of caspase3 (), and were studied in mouse hippocampal mHippoE-2 cell line and in the hippocampus of MK-801 animal schizophrenia model with the aim to provide evidence that antipsychotics may affect the activity of apoptosis-related markers. mHippoE-2 cells were incubated with MK-801 (20 µM), HAL (10 µM), and OLA (10 µM) alone or combined, MK-801+HAL/OLA, for 24, 48, and 72 h.

Effect of Haloperidol and Olanzapine on Hippocampal Cells' Proliferation in Animal Model of Schizophrenia.

Aberrant neurogenesis in the subventricular zone (SVZ) and hippocampus (HIP) contributes to schizophrenia pathogenesis. Haloperidol (HAL) and olanzapine (OLA), commonly prescribed antipsychotics for schizophrenia treatment, affect neurogenesis too. The effect of HAL and OLA on an mHippoE-2 cell line was studied in vitro where we measured the cell number and projection length.

The role of selected postsynaptic scaffolding proteins at glutamatergic synapses in autism-related animal models.

Pathological changes in synapse formation, plasticity, and development are caused by altered trafficking and assembly of postsynaptic scaffolding proteins at sites of glutamatergic and gamma-aminobutyric acid (GABA)ergic synapses, suggesting their involvement in the etiology of neurodevelopmental disorders, including autism. Several autism-related mouse models have been developed in recent years for studying molecular, cellular, and behavioural defects in order to understand the etiology of autism and test the potential treatment strategies. In this review, we explain the role of alterations in selected postsynaptic scaffolding proteins in relevant transgene autism-like mouse models.

Gene expression levels of DNA methyltransferase enzymes in -deficient mouse model of autism during early development.

The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 ()-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms.

Photodynamic therapy of multidrug resistant leukemic murine cells by 3,6-bis(alkylthiourea)acridine hydrochlorides.

Efforts to overcome multidrug resistance in cancer have led to the development of several novel strategies including photodynamic therapy (PDT). PDT is based on the use of photosensitizers (PSs) photoactivation, which causes the formation of reactive oxygen species that can induce cell death. In the last decade, the development of new PSs has been significantly accelerated.

Shank3 Deficiency is Associated With Altered Profile of Neurotransmission Markers in Pups and Adult Mice.

Alterations in the balance between excitation and inhibition, especially in the brain's critical developmental periods, are considered an integral part of the pathophysiology of autism. However, the precise mechanisms have not yet been established. SH3 and multiple Ankyrin repeat domains 3 (Shank3) deficient mice represent a well-established transgenic model of a neurodevelopmental disorder with autistic symptomatology.

The effects of testosterone on gene expression of cell-adhesion molecules and scaffolding proteins: The role of sex in early development.

Sex-specific differences in brain plasticity appear to be organised by testosterone, which is particularly important during the early stages of development. The main purpose of the present study was to examine the sex differences in mRNA and protein levels of selected cell-adhesion molecules and scaffolding proteins on postnatal days 5 (P5) and 9 (P9) in the rat hippocampus, as well as evaluate the effects of testosterone treatment (100 nM, 48 hr) on synaptic proteins in SH-SY5Y (neuron-like) and U-87MG (astrocyte-like) cells. The gene expression levels of Neuroligin 3 and 'SH3 and multiple ankyrin repeat domains protein' 1 and 3 (SHANK1 and SHANK3) were significantly lower in males compared to females at P5.

The epigenetic regulation of synaptic genes contributes to the etiology of autism.

Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins.

The impact of oxytocin on neurite outgrowth and synaptic proteins in Magel2-deficient mice.

Oxytocin contributes to the regulation of cytoskeletal and synaptic proteins and could, therefore, affect the mechanisms of neurodevelopmental disorders, including autism. Both the Prader-Willi syndrome and Schaaf-Yang syndrome exhibit autistic symptoms involving the MAGEL2 gene. Magel2-deficient mice show a deficit in social behavior that is rescued following the postnatal administration of oxytocin.

Abnormal neuronal morphology and altered synaptic proteins are restored by oxytocin in autism-related SHANK3 deficient model.

Oxytocin has been suggested as a potential therapeutic agent in autism and other neuropsychiatric conditions. Although, the link between the deficit in "SH3 domain and ankyrin repeat containing protein 3" (SHANK3) and autism spectrum disorders is highly studied topic, developmental mechanisms are still poorly understood. In this study, we clearly confirm that SHANK3 deficiency is accompanied with abnormalities in neurite number and length, which are reversed by oxytocin treatment (1 μM, 48h) in primary hippocampal neurons.

Neuronal morphology alterations in autism and possible role of oxytocin.

Current understanding of the neuroanatomical abnormalities in autism includes gross anatomical changes in several brain areas and microstructural alterations in neuronal cells as well. There are many controversies in the interpretation of the imaging data, evaluation of volume and size of particular brain areas, and their functional translation into a broad autism phenotype. Critical questions of neuronal pathology in autism include the concept of the reversible plasticity of morphological changes, volume alterations of brain areas, and both short- and long-term consequences of adverse events present during the brain development.

Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection.

Aberrant regulation of oxytocin signaling is associated with the etiology of neurodevelopmental disorders. Synaptic dysfunctions in neurodevelopmental disorders are becoming increasingly known, and their pathogenic mechanisms could be a target of potential therapeutic intervention. Therefore, it is important to pay attention to the role of oxytocin and its receptor in synapse structure, function, and neuron connectivity.

Abnormalities in interactions of Rho GTPases with scaffolding proteins contribute to neurodevelopmental disorders.

Accumulating evidence suggests that Rho GTPases, together with scaffolding SHANK proteins, and associated signaling pathways play a role in the development of autism symptoms in various conditions. Research data have brought information on multiple intracellular signaling pathways, including Rho-associated protein kinases and serine/threonine-protein kinases involved in cytoskeleton rearranging. Alterations in downstream effectors of GTPase signaling pathways are associated with neurodevelopmental disorders.

Polysulfides and products of HS/S-nitrosoglutathione in comparison to HS, glutathione and antioxidant Trolox are potent scavengers of superoxide anion radical and produce hydroxyl radical by decomposition of HO.

Exogenous and endogenously produced sulfide derivatives, such as HS/HS/S, polysulfides and products of the HS/S-nitrosoglutathione interaction (S/GSNO), affect numerous biological processes in which superoxide anion (O) and hydroxyl (OH) radicals play an important role. Their cytoprotective-antioxidant and contrasting pro-oxidant-toxic effects have been reported. Therefore, the aim of our work was to contribute to resolving this apparent inconsistency by studying sulfide derivatives/free radical interactions and their consequent biological effects compared to the antioxidants glutathione (GSH) and Trolox.

The Role of Hypothalamic Neuropeptides in Neurogenesis and Neuritogenesis.

The hypothalamus is a source of neural progenitor cells which give rise to different populations of specialized and differentiated cells during brain development. Newly formed neurons in the hypothalamus can synthesize and release various neuropeptides. Although term neuropeptide recently undergoes redefinition, small-size hypothalamic neuropeptides remain major signaling molecules mediating short- and long-term effects on brain development.

Are Molecules Involved in Neuritogenesis and Axon Guidance Related to Autism Pathogenesis?

Autism spectrum disorder is a heterogeneous disease, and numerous alterations of gene expression come into play to attempt to explain potential molecular and pathophysiological causes. Abnormalities of brain development and connectivity associated with alterations in cytoskeletal rearrangement, neuritogenesis and elongation of axons and dendrites might represent or contribute to the structural basis of autism pathology. Slit/Robo signaling regulates cytoskeletal remodeling related to axonal and dendritic branching.

Intracerebroventricular oxytocin administration in rats enhances object recognition and increases expression of neurotrophins, microtubule-associated protein 2, and synapsin I.

Brain oxytocin regulates a variety of social and affiliative behaviors and affects also learning and memory. However, mechanisms of its action at the level of neuronal circuits are not fully understood. The present study tests the hypothesis that molecular factors required for memory formation and synaptic plasticity, including brain-derived neurotrophic factor, neural growth factor, nestin, microtubule-associated protein 2 (MAP2), and synapsin I, are enhanced by central administration of oxytocin.

Neonatal manipulation of oxytocin prevents lipopolysaccharide-induced decrease in gene expression of growth factors in two developmental stages of the female rat.

Oxytocin production and secretion is important for early development of the brain. Long-term consequences of manipulation of oxytocin system might include changes in markers of brain plasticity - cytoskeletal proteins and neurotrophins. The aim of the present study was (1) to determine whether neonatal oxytocin administration affects gene expression of nestin, microtubule-associated protein-2 (MAP-2), brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of two developmental stages of rat and (2) to evaluate whether neonatal oxytocin administration protects against lipopolysaccharide (LPS) induced inflammation.