Developmental brain injury and social determinants of health: opportunities to combine preclinical models for mechanistic insights into recovery
Epidemiological studies show that social determinants of health are amongst the strongest factors associated with developmental outcomes after prenatal and perinatal brain injuries, even when controlling for the severity of the initial injury. Elevated socioeconomic status and a higher level of parental education correlate with improved neurologic function after premature birth. Conversely, children experiencing early life adversity have worse outcomes after developmental brain injuries. Animal models have provided vital insight into mechanisms perturbed by developmental brain injuries, which have indicated directions for ...
Source: Developmental Neuroscience - April 20, 2023 Category: Neuroscience Source Type: research
Hippo Pathway in Schwann Cells and Regeneration of Peripheral Nervous System
Hippo pathway is an evolutionarily conserved signaling pathway consisting of a series of MST/LATS kinase complexes. Its key transcriptional co-activators YAP and TAZ regulate transcription factors such as TEAD family to direct gene expression. The regulation of Hippo pathway, especially the nuclear level change of YAP and TAZ, significantly influences the cell fate switching from proliferation to differentiation, regeneration and post-injury repair. This review outlines the main findings of Hippo pathway in peripheral nerve development, regeneration, and tumorigenesis, especially the studies in Schwann cells. We also summa...
Source: Developmental Neuroscience - April 20, 2023 Category: Neuroscience Source Type: research
In utero exposure to valproic acid throughout pregnancy causes phenotypes of autism in offspring mice
Valproic acid (VPA) is an antiepileptic drug that inhibits the epileptic activity of neurons mainly by inhibiting sodium channels and GABA transaminase. VPA is also known to inhibit histone deacetylases, which epigenetically modify the cell proliferation/differentiation characteristics of stem/progenitor cells within developing tissues. Recent clinical studies in humans have indicated that VPA exposure in utero increases the risk of autistic features and intellectual disabilities in offspring; we previously reported that low-dose VPA exposure in utero throughout pregnancy increases the production of projection neurons from...
Source: Developmental Neuroscience - April 12, 2023 Category: Neuroscience Source Type: research
Sexual dimorphism in the closure of the hippocampal postnatal critical period of synaptic plasticity after intrauterine growth restriction – link to oligodendrocyte and glial dysregulation
Intrauterine growth restriction (IUGR) resulting from hypertensive disease of pregnancy (HDP) leads to sexually dimorphic hippocampal-dependent cognitive and memory impairment in humans. In our translationally-relevant mouse model of IUGR incited by HDP, we have previously shown that the synaptic development in the dorsal hippocampus including GABAergic development, NPTX2+ excitatory synaptic formation, axonal myelination, and perineural net (PNN) formation, were perturbed by IUGR at adolescent equivalence in humans (P40). The persistence of these disturbances through early adulthood and the potential upstream mechanisms a...
Source: Developmental Neuroscience - April 5, 2023 Category: Neuroscience Source Type: research
Beyond the rainbow: a review of advanced lineage tracing methodologies for interrogating the initiation, evolution, and recurrence of brain tumors
The mammalian forebrain is perhaps the pinnacle of evolution and one of the most complex structures in known existence. The origin of this complexity and diversity partly lies in dynamic behavior of progenitors during embryonic neural development, all of which is under the control of regulatory mechanisms that ensure all the elements end up in the right place at the right time. Historically, dye-base, histochemical, enzymatic, or fluorescent lineage tracing techniques have been used deconvolute developmental dynamics in tissues and cells. Technical limitations resulted from a restrictive number of fluorophores, the half-li...
Source: Developmental Neuroscience - April 4, 2023 Category: Neuroscience Source Type: research
Prenatal stress induces translational disruption associated with myelination deficits
Conclusion: The deficits early in the process of maturation of myelination indicates that the reduced myelination observed at childhood equivalence in previous studies begins in fetal life. This negative programming persists into childhood potentially due to dysregulation of MBP translation processes. Expression patterns of neurosteroidogenic enzymes in the placenta at term following stress may identify at-risk fetuses that have been exposed to a stressful in utero environment. (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 31, 2023 Category: Neuroscience Source Type: research
Dendrimer-Conjugated Glutamate Carboxypeptidase II Inhibitor Restores Microglial Changes in a Rabbit Model of Cerebral Palsy
We have previously shown that maternal endotoxin exposure leads to a phenotype of cerebral palsy and pro-inflammatory microglia in the brain in neonatal rabbits. “Activated” microglia overexpress the enzyme glutamate carboxypeptidase II (GCPII) that hydrolyzes N-acetylaspartylglutamate to N-acetylaspartate and glutamate, and we have shown previously that inhibiting microglial GCPII is neuroprotective. Glutamate-induced injury and associated immune signal ing can alter microglial responses including microglial process movements for surveillance and phagocytosis. We hypothesize that inhibition of GCPII activity could alt...
Source: Developmental Neuroscience - March 29, 2023 Category: Neuroscience Source Type: research
Dendrimer conjugated glutamate carboxypeptidase II inhibitor restores microglial changes in a rabbit model of cerebral palsy
We have previously shown that maternal endotoxin exposure leads to a phenotype of cerebral palsy and pro-inflammatory microglia in the brain in neonatal rabbits. ‘Activated’ microglia overexpress the enzyme glutamate carboxypeptidase II (GCPII) that hydrolyzes N-acetylaspartylglutamate (NAAG) to N-acetylaspartate (NAA) and glutamate, and we have shown previously that inhibiting microglial GCPII is neuroprotective. Glutamate-induced injury and associated immune signaling can alter microglial responses including microglial process movements for surveillance and phagocytosis. We hypothesize that inhibition of GCPII activi...
Source: Developmental Neuroscience - March 29, 2023 Category: Neuroscience Source Type: research
A Proposed Human Structural Brain Connectivity Matrix in the Center for Morphometric Analysis Harvard-Oxford Atlas Framework: A Historical Perspective and Future Direction for Enhancing the Precision of Human Structural Connectivity with a Novel Neuroanatomical Typology
A complete structural definition of the human nervous system must include delineation of its wiring diagram (e.g., Swanson LW. Brain architecture: understanding the basic plan, 2012). The complete formulation of the human brain circuit diagram (BCD [Front Neuroanat. 2020;14:18]) has been hampered by an inability to determine connections in their entirety (i.e., not only pathway stems but also origins and terminations). From a structural point of view, a neuroanatomic formulation of the BCD should include the origins and terminations of each fiber tract as well as the topographic course of the fiber tract in three dimension...
Source: Developmental Neuroscience - March 28, 2023 Category: Neuroscience Source Type: research
A Proposed Human Structural Brain Connectivity Matrix
in the Center for Morphometric Analysis Harvard-Oxford Atlas Framework:
A historical perspective and future direction for enhancing the precision of
human structural connectivity with a novel neuroanatomical typology.
A complete structural definition of the human nervous system must include delineation of its wiring diagram (e.g., [1]). The complete formulation of the human brain circuit diagram (BCD; [2]) has been hampered by an inability to determine connections in their entirety (i.e., not only pathway stems, but also origins and terminations). From a structural point of view, a neuroanatomic formulation of the BCD should include the origins and terminations of each fiber tract as well as the topographic course of the fiber tract in three dimensions. Classic neuroanatomical studies have provided trajectory information for pathway ste...
Source: Developmental Neuroscience - March 28, 2023 Category: Neuroscience Source Type: research
The Outcomes of Maternal Immune Activation Induced with the Viral Mimetic Poly I:C on Microglia in Exposed Rodent Offspring
Maternal immune activation (MIA) can result from a variety of maternal inflammatory factors, including metabolic disorders, nutritional deficits, infections, and psychosocial stress. MIA has been consistently recognized as a major risk factor for neurodevelopmental disorders, and this association seems to be especially important for viral infections, as viral exposure during pregnancy was associated with a higher risk of developing neurodevelopmental disorders, such as schizophrenia. In MIA, the gestational parent ’s inflammatory response to an immune stimulus alters or interrupts fetal development, triggering neurodevel...
Source: Developmental Neuroscience - March 21, 2023 Category: Neuroscience Source Type: research
Paternal Deprivation and Female Biparental Family Rearing Induce Dendritic and Synaptic Changes in < i > Octodon degus < /i > : II. Nucleus Accumbens
While the majority of studies on the importance of parental caregiving on offspring behavioral and brain development focus on the role of the mother, the paternal contribution is still an understudied topic. We investigated if growing up without paternal care affects dendritic and synaptic development in the nucleus accumbens of male and female offspring and if replacement of the father by a female caregiver “compensates” the impact of paternal deprivation. We compared (a) biparental rearing by father and mother, (b) monoparental care by a single mother, and (c) biparental rearing by two female caregivers. Quantitative...
Source: Developmental Neuroscience - March 9, 2023 Category: Neuroscience Source Type: research
Paternal Deprivation and Female Biparental Family Rearing Induce Dendritic and Synaptic Changes in Octodon degus: II. Nucleus Accumbens
While the majority of studies on the importance of parental caregiving on offspring behavioral and brain development focus on the role of the mother, the paternal contribution is still an understudied topic. We investigated if growing up without paternal care affects dendritic and synaptic development in the nucleus accumbens of male and female offspring, and if replacement of the father by a female caregiver “compensates” the impact of paternal deprivation. We compared a) biparental rearing by father and mother b) mono-parental care by a single mother and c) biparental rearing by two female caregivers. Quantitative an...
Source: Developmental Neuroscience - March 9, 2023 Category: Neuroscience Source Type: research
