Biology of GDNF and its receptors — Relevance for disorders of the central nervous system
Neurobiology of Disease · 2016
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Astrocytes: biology and pathology
Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.
Factors influencing knowledge about childhood autism among final year undergraduate Medical, Nursing and Psychology students of University of Nigeria, Enugu State, Nigeria
BACKGROUND: Knowledge and awareness about childhood autism is low among health care workers and the general populace in Nigeria. Poor knowledge about childhood autism among final year medical, nursing and psychology students who would form tomorrow's child health care professionals can compromise early recognition and interventions that are known to improve prognosis in childhood autism. Educational factors that could be influencing knowledge about childhood autism among these future health care professionals are unknown. This study assessed knowledge about childhood autism among final year undergraduate medical, nursing and psychology students in south-eastern Nigeria and determined the factors that could be influencing such knowledge. METHODS: One hundred final year undergraduate students were randomly selected from each of the Departments of Medicine, Nursing Science and Psychology respectively of University of Nigeria, Enugu State, Nigeria making a sample size of three hundred. A socio-demographic questionnaire and knowledge about childhood autism among health workers (KCAHW) questionnaire were administered to the students. RESULTS: The total mean score for the three groups of students on the KCAHW questionnaire was 10.67+/-3.73 out of a possible total score of 19, with medical, nursing and psychology students having total mean scores of 12.24+/-3.24, 10.76+/-3.50 and 9.01+/-3.76 respectively. The mean scores for the three groups showed statistically significant difference for domain 1 (p=0.000), domain 3 (p=0.029), domain 4 (p=0.000) and total score (p=0.000), with medical students more likely to recognise symptoms and signs of autism compared to nursing and psychology students. The mean score in domain 2 did not show statistically significant difference among the three groups (p=0.769). The total score on the KCAHW questionnaire is positively correlated with the number of weeks of posting in psychiatry (r=0.319, p=0.000) and the number of weeks of posting in paediatrics (r=0.372, p=0.000). The total score is also positively correlated with the number of credit hours of lectures in psychiatry/abnormal psychology (r=0.324, p=0.000) and the number of credit hours of lectures in paediatrics (r=0.372, p=0.000). The field of study also influenced knowledge about childhood autism (p=0.000). CONCLUSION: Peculiar situation in this environment as signified by inadequate human resources needed in the area of clinical psychology training often times necessitates employing first degree graduates in psychology into clinical positions. This calls for additional exposure of the undergraduate psychology students to training curriculum aimed at improving their early recognition of symptoms of autism spectrum disorders in this environment.
Gene-Environment Interactions and Epigenetic Regulation in Autism Etiology through Multi-Omics Integration and Computational Biology Approaches
Autism Spectrum Disorder (ASD) is a multifactorial neurodevelopmental condition characterized by substantial genetic heterogeneity and complex environmental influences. Emerging evidence suggests that gene-environment interactions, mediated through dynamic epigenetic mechanisms, play a critical role in modulating neurodevelopmental trajectories implicated in ASD. This review synthesizes current advances in understanding the etiological interplay between genetic variants, environmental exposures, and epigenetic regulation, with a focus on DNA methylation, histone modifications, and non-coding RNAs. We explore how these layers of molecular control intersect to dysregulate neurodevelopmental gene networks and contribute to ASD pathophysiology. Central to this investigation is the integration of multi-omics platforms— encompassing genomics, transcriptomics, epigenomics, proteomics, and metabolomics—supported by computational biology, machine learning, and systems-level modeling frameworks. These technologies facilitate the identification of molecular subtypes, predictive biomarkers, and regulatory circuits associated with ASD. Furthermore, we examine the translational implications of these findings in the context of precision medicine, including early diagnosis, patient stratification, and individualized therapeutic development. Despite the challenges of data heterogeneity, scalability, and interpretability, the integration of high-dimensional biological data holds transformative potential for elucidating ASD etiology and advancing targeted interventions.
