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Developmental Diseases of the Nervous System
Published in Philip B. Gorelick, Fernando D. Testai, Graeme J. Hankey, Joanna M. Wardlaw, Hankey's Clinical Neurology, 2020
James H. Tonsgard, Nikolas Mata-Machado
Most LISI mutations are de novo, with a low risk of recurrence. However, some parents have a balanced translocation involving the LISI gene with a higher risk of recurrence. Patients with lissencephaly may also have a mutation in the DCX gene or in the TUBA1A gene. The DCX gene is located on the X chromosome; a mutation in one of the X chromosomes in females results in subcortical band heterotopia (discussed below), whereas males inheriting the DCX mutation have classical lissencephaly. TUBA1A mutations are autosomal dominant disorders. Three-quarters of the patients with classical lissencephaly have a mutation either in the LISI gene or the DCX gene.
Human Immunodeficiency Virus Neuropathogenesis
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
Adult neurogenesis (ANG) was initially thought to occur only in rodents. Recent findings show that ANG also takes place in humans and other primates (Eriksson et al. 1998). ANG is important for maintaining the homeostatic state of CNS and is involved in learning, memory, olfaction, and anxiety-related behaviors (Revest et al. 2009). ANG has been reported to get perturbed in HAND (Rodriguez et al. 2008; Taupin 2009). Astrocytes provide trophic support to both mature and immature neurons, but this support gets impaired in cases of HIV infection in the brain and that restricts the proliferation and migration of Neural Progenitor Cells (NPCs) (Eriksson et al. 1998). Maturation and differentiation of NPCs are dependent on cell cycle regulation (Herrup and Yang 2007). Disruption at the level of cell cycle proteins such as the transcription factor, E2F1, and its regulator, the retinoblastoma gene, are reported to be dysregulated in patients having HAND (Hoglinger et al. 2007). Another cell cycle protein doublecortin (dcx) (microtubule protein) expressed in immature neurons was shown to be disrupted in HAND (Herrup and Yang 2007). Dysregulated expression of E2F1 disrupts the dcx, which ultimately leads to the disruption in ANG. Disruption of ANG and its molecular regulation trims down the plasticity of the CNS, which leads to devastating consequences in brain regions assaulted by HIV-induced toxicity (Karl et al. 2005).
Neurogenesis in the Adult and Aging Brain
Published in David R. Riddle, Brain Aging, 2007
David R. Riddle, Robin J. Lichtenwalner
Although the survival of newborn cells in neurogenic regions appears to be unaffected by age, the percentage of newborn cells that become neurons is much lower in middle-aged and old animals than in young adults (e.g., [12, 56, 58, 60, 84]). When examined approximately 4 weeks after BrdU labeling, the percentage of newborn cells in the DG that express neuronal markers is reduced by about 60% between young adulthood and middle-age in rats [58, 84], and by 40% or more in mice [56, 60]. Thus, in aged animals, the overall reduction in the proliferation of progenitor cells is compounded by a decrease in the fraction of cells that are produced that become neurons. The aging-related decrease in the development of newborn neurons may not reflect a decrease in initial commitment to a neuronal lineage, however, because a comparable percentage of newborn cells expresses the neuroblast marker doublecortin (Dcx) 24 hours after BrdU labeling [84]. The subsequent development of new neurons is compromised in older animals, however, because both the rate of migration into the granule cell layer and the rate of structural maturation are slowed in middle-aged and old rats, compared to young adults [84].
Grape seed extract effects on hippocampal neurogenesis, synaptogenesis and dark neurons production in old mice. Can this extract improve learning and memory in aged animals?
Published in Nutritional Neuroscience, 2022
Seyed Hamidreza Rastegar-moghaddam, Maryam Bigham, Mahmoud Hosseini, Alireza Ebrahimzadeh-bideskan, Amir Mohammad Malvandi, Abbas Mohammadipour
Neurogenesis in adults’ brains is limited to subventricular and subgranular zones [5,6,37]. The Subgranular zone is located beneath the granular cells of the DG and plays a crucial role in the replacement of hippocampal neurons throughout life. The higher the neurogenesis in this area helps to have the better cognitive performance [38]. In the current study, we used the DCX as a maker to study neurogenesis. DCX is a microtubule-associated protein, which is explicitly expressed only in neuronal progenitor cells and disappears in the mature neurons [39]. Thus, identifying this marker in an area of the brain is associated with neurogenesis in that area [5,39]. In the aged brain, the hippocampal neurogenesis rate decreases and leads to memory loss [40–42]. Our results showed that GSE administration increased the neurogenesis in hippocampi of aged mice.
Impaired response to sleep deprivation in heterozygous Disc1 mutant mice
Published in The World Journal of Biological Psychiatry, 2022
Chih-Yu Tsao, Li-Heng Tuan, Lukas Jyuhn-Hsiarn Lee, Chih-Min Liu, Hai-Gwo Hwu, Li-Jen Lee
We further characterised the features of doublecortin (DCX)-positive SGZ cells (Figure 5(A)). DCX is a microtubule-associated protein important for neuronal migration and has been commonly used as a marker of immature neurons. The density of DCX-positive neurons in the SGZ was similar between WT and Het mice and was not altered by SD or Disc1 mutation (Figure 5(B)). The maturation process of newly generated DG granule cells could be evaluated by the morphology of DCX-positive neurons (Plümpe et al. 2006). There was a higher ratio of cells in the proliferative stage in WT-SD mice (45%) than in control (WT-BP) mice (33%) (F(1, 9)=21.062, p = 0.001), indicating a sign of SD-induced developmental delay. The ratio of cells in the later post-mitotic stage was decreased in Het-SD mice (30%) compared with Het-BP group (42%) (F(1, 9)=8.565, p = 0.017) (Figure 5(C)), suggesting a sign of retardation in neuronal maturation. Here we demonstrated that the maturation process of newly generated DG neurons was affected by 72-hour SD. Collectively, our results suggested that the deleterious effects of SD on hippocampal neurogenesis seem to be more profound in Disc1 Het mice.
Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high-fat diet
Published in Nutritional Neuroscience, 2019
Amanda N. Carey, Kelsea R. Gildawie, Abigail Rovnak, Nopporn Thangthaeng, Derek R. Fisher, Barbara Shukitt-Hale
We found a similar pattern of results when we examined DCX-positive cells in the dentate gyrus of the hippocampus. DCX stains immature neurons and is reflective of neurogenesis in the adult brain.63 There was a significant increase in the number of DCX-positive cells in mice fed the HFD + blueberry, but not the mice fed the other diets. Furthermore, mice fed HFD + BB had greater dendritic arborization of the DCX-positive neurons than HFD-fed mice. This enhanced neurogenesis and morphology suggests greater plasticity in the hippocampi of the mice fed HFD + blueberry and is consistent with previous research that found that blueberry supplementation in aged rats was associated with increased neurogenesis.31,38 Furthermore, this is consistent with the increase in BDNF; BDNF plays an important role in promoting the differentiation, growth, and survival of new neurons in the hippocampus.7,64 The influence of BDNF could also explain why the newly generated neurons in the hippocampus were more developed, with more dendritic arborization, in the HFD + blueberry group.