Human Immunodeficiency Virus Neuropathogenesis
Sunit K. Singh, Daniel Růžek in 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
David R. Riddle in Brain Aging, 2007
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].
Paediatric Neurology
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
Lissencephaly (literally ‘smooth brain’) refers to a disorder where there is a lack of gyral and sulcal development. It has now been recognized that subcortical band heterotopia (SBH) form part of the classical lissencephaly spectrum with a common genetic basis. Mutations in several genes, LIS1, DCX (doublecortin) or XLIS, and RLN (reelin) have been identified as producing different patterns of abnormality, the latter being associated with additional cerebellar hypoplasia. On occasions, it is these additional abnormalities either in the CNS or outside that may define the disorder.
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.
Gene expression changes in rat brain regions after 7- and 28 days inhalation exposure to exhaust emissions from 1st and 2nd generation biodiesel fuels - The FuelHealth project
Published in Inhalation Toxicology, 2018
Renate Valand, Pål Magnusson, Katarzyna Dziendzikowska, Malgorzata Gajewska, Jacek Wilczak, Michał Oczkowski, Dariusz Kamola, Tomasz Królikowski, Marcin Kruszewski, Anna Lankoff, Remigiusz Mruk, Dag Marcus Eide, Rafał Sapierzyński, Joanna Gromadzka-Ostrowska, Nur Duale, Johan Øvrevik, Oddvar Myhre
Auts2, Dcx and Vamp2 are important for normal brain function, and dysregulation of these genes are associated with cognitive deficits or neurological diseases. Cytosolic AUTS2 is reported to regulate actin cytoskeleton to control neuronal migration and neurite extension, while nuclear AUTS2 controls transcription of various genes (Hori & Hoshino, 2017). Dcx codes for the protein doublecortin and mutations in this gene in humans are associated with severe mental retardation and refractory epilepsy (Guerrini & Marini, 2006). Also, DCX that enriches in neurons during adult neurogenesis, especially those in the subgranular zone in hippocampus are important for contextual learning and memory (Leuner et al., 2006). Neurotransmission depends upon the regulated fusion of neurotransmitter-laden vesicles with the presynaptic plasma membrane, where VAMP2 is an essential component of the fusion machinery.
Harnessing neuroplasticity: modern approaches and clinical future
Published in International Journal of Neuroscience, 2018
Andrew Octavian Sasmita, Joshua Kuruvilla, Anna Pick Kiong Ling
Modulation of neuronal migratory and guiding proteins such as doublecortin (DCX) [95,110] has been repeatedly shown to successfully promote synaptogenesis and neurogenesis upon their overexpression in cases of TBI. BDNF is another majorly studied molecule implicated in modulation of neurogenesis at a dose-dependent manner [89] via tropomyosin-related kinase B coupled with phospholipase Cγ (PLCγ), phosphatidylinositol 3-kinase (PI3K), Akt, Ras and Etv1 pathways [90–92]. With regards to ion channels involved in signal relay, the existing antidepressant, spadin, targets the potassium channel protein TREK-1, effectively blocking its activity and inducing neurogenesis via the CREB pathway [82]. The utilization of other antidepressants has been studied to induce neurogenesis in applications which go beyond depression and psychological problems, such as sertraline which increased neuroblasts and mature neurons, indicating neuronal differentiation through glucocorticoid receptor mechanisms [83]. Fluoxetine, a type of selective serotonin reuptake inhibitors, was also reported to accelerate maturation of neurons and promote synaptic plasticity in hippocampal granule cells [84]. The effect of fluoxetine is also more pronounced in the chronic corticosterone in mice models [111].