The mechanism of degeneration of striatal neuronal subtypes in Huntington disease

Abstract

The pattern of neurodegeneration in Huntington’s disease (HD) is very characteristic of regional locations as well as that of neuronal types in striatum. The different striatal neuronal populations demonstrate different degree of degeneration in response to various pathological events in HD. In the striatum, medium spiny GABA neurons (MSN) are preferentially degenerate while others are relatively spared. Vulnerability of specific neuronal populations within the striatum to pathological events constitutes an important hallmark of degeneration in HD. In an attempt to explain a likely mechanism of degeneration of striatal neuronal populations in HD, possible causes underlying differential vulnerability of neuronal subtypes to excitoxic insults and neurotrophic factors are discussed in this paper.

Terapeutic Potential of Microencapsulated Sertoli Cells in Huntington Disease

“…It is likely that MC-SC-derived immunomodulatory factors [4] acted on microglial cells preventing their overactivation, thereby decreasing pro-inflammatory molecule levels. Moreover, defective regulation of growth factors, such as brainderived neurotrophic factor (BDNF) and glial-derived neurotrophic factor (GDNF), affects CNS function and contributes to the pathogenesis of HD [2]. It is known that intrastriatal injection of "naked" SC enhances survival of dopaminergic neurons and induces an extensive neurite outgrowth by GDNF, a SC secretory product [4].…”

Endocannabinoid system in neurodegenerative disorders

“…It is very clear that cannabinoid signal becomes hypofunctional in the basal ganglia in HD. However, it has also been suggested that loss of CB1R may be initially related to the progressive and selective loss of medium spiny GABAergic neurons in the striatum, where these receptors are abundant (Rikani et al 2014). Studies using R6/2 mice at presymptomatic ages showed impairment of the sensitivity of striatal GABA synapses to cannabinoid stimulation (Centonze et al 2005).…”

Regulatory network underlying alterations of gene expression in early death of Huntington's disease

“…Speci cally, it was increasingly expressed in the embryonic brain, with its encoded β3 subunit involved in the biological processes of stem cell differentiation, assembly and tra cking of GABA receptor [36,37]. The inhibitory synaptic transmission mediated by GABA receptor were susceptible to the accumulation of mutant huntingtin, leading to early degeneration of GABAergic neurons in the striatum of HD patients [38]. Indeed, many of the manifestations that were emerged early in HD, such as hippocampal-dependent learning and memory impairment, were considerably attributed to the weakened inhibitory GABAergic transmission veri ed in a HD mouse model [25].…”