HIV on the brain: is neurosignalling damage irreversible even on antiretroviral therapy?
HIV on the brain: is neurosignalling damage irreversible even on antiretroviral therapy?
复制标题
大脑上的艾滋病毒：即使在抗逆转录病毒疗法上，神经信号损害是否不可逆？
DOI：
10.1097/qad.0000000000002957
复制
发表时间：
2021-07-15
期刊：
影响因子：
--
通讯作者：
Reeves RK
中科院分区：
文献类型：
--
作者：
Tan CS;Reeves RK
Even with successful antiretroviral therapies (ARTs), comorbidities in persons with HIV (PWH) remain high. Among these are a range of neurocognitive impairments presenting within the full spectrum under HIV-associated neurocognitive disorder (HAND), which can range from asymptomatic neurocognitive impairment to the severe neurological dysfunction affecting activities of daily living [1]. Multiple causes associated with HIV disease may exist and the underlying mechanisms remain poorly defined, but neurocognitive dysfunction is thought to be largely driven by neuroinflammation and dysregulation of neural and immune networks in the central nervous system (CNS)[2]. Also, alcohol abuse in addition to HIV infection has the potential to further decrease neurocognition, though study results can be conflicting: some found no correlation of days of intoxication to degree of neurocognitive impairment [3], but PWH users of alcohol also display lower than average neurocognition [4]. Although suppression of virus by ART can potentially dampen inciting factors driving neuroinflammation, it is unclear if treatment intercedes on all facets of neuroinflammation and restores neural connections.In this issue, a new study by Maxi et al.[5] uses a simian immunodeficiency virus (SIV)-infected rhesus macaque model wherein they study the effects of infection as well as binge alcohol use on measures of neuroinflammation. The investigators further evaluate the impact of ART in this model to reduce inflammation and restore neurosignals. Although ART reduced most measures of neuroinflammation, including IBA1, CX3CR1 and GFAP gene expression in the frontal cortex, and CD74 and CD11ß in the basal ganglia, brain-derived neurotrophic factor (BDNF) signalling was not restored in either anatomical location. BDNF, a member of the neurotrophin family, is one of the most abundant neurosynaptic factors in the brain and mediates CNS plasticity. Loss of BDNF is associated with memory and learning deficits, and has been associated with increased incidences of depression and Alzheimer's disease. Importantly, multiple studies have shown that loss of BDNF also correlates with severity of HAND [6], where cerebrospinal fluid BDNF levels were significantly lower in PWH with HIV-dementia when compared with PWH without dementia [7]. Serum BDNF levels also correlated directly with performance on neurocognitive tests of executive functions and memory [8]. In a cross-sectional study of 350 PWH and 50 HIV seronegative individuals, ART did not alter serum levels of BDNF in PWH, although CNS BDNF values were not assessed [9]. Furthermore, alcohol exposure, specifically beer and liquor, was also associated with decreased serum BDNF in PWH in that study. Although moderate alcohol ingestion can acutely trigger BDNF release, which prevents progression to compulsive alcohol consumption, chronic heavy alcohol consumption eventually disrupts the protective functions of BDNF [10, 11]. Chronic alcohol exposure may further exacerbate the reduction of BDNF in the brain of PWH. Additional knowledge is lacking on BDNF regulation in terms of timing and duration of alcohol and HIV exposures.
