Elhabbari Kaoutar, Sireci Siran, Rothermel Markus, Brunert Daniela
Institute of Physiology, RG Neurophysiology and Optogenetics, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany.
Front Neurosci. 2024 Dec 16;18:1503069. doi: 10.3389/fnins.2024.1503069. eCollection 2024.
Cognitive function in healthy aging and neurodegenerative diseases like Alzheimer's disease (AD) correlates to olfactory performance. Aging and disease progression both show marked olfactory deficits in humans and rodents. As a clear understanding of what causes olfactory deficits is still missing, research on this topic is paramount to diagnostics and early intervention therapy. A recent development of this research is focusing on GABAergic interneurons. Both aging and AD show a change in excitation/inhibition balance, indicating reduced inhibitory network functions. In the olfactory system, inhibition has an especially prominent role in processing information, as the olfactory bulb (OB), the first relay station of olfactory information in the brain, contains an unusually high number of inhibitory interneurons. This review summarizes the current knowledge on inhibitory interneurons at the level of the OB and the primary olfactory cortices to gain an overview of how these neurons might influence olfactory behavior. We also compare changes in interneuron composition in different olfactory brain areas between healthy aging and AD as the most common neurodegenerative disease. We find that pathophysiological changes in olfactory areas mirror findings from hippocampal and cortical regions that describe a marked cell loss for GABAergic interneurons in AD but not aging. Rather than differences in brain areas, differences in vulnerability were shown for different interneuron populations through all olfactory regions, with somatostatin-positive cells most strongly affected.
健康衰老以及诸如阿尔茨海默病（AD）等神经退行性疾病中的认知功能与嗅觉表现相关。衰老和疾病进展在人类和啮齿动物中均表现出明显的嗅觉缺陷。由于对嗅觉缺陷的成因仍缺乏清晰认识，因此关于这一主题的研究对于诊断和早期干预治疗至关重要。该研究的一个最新进展聚焦于γ-氨基丁酸（GABA）能中间神经元。衰老和AD均显示出兴奋/抑制平衡的变化，表明抑制性网络功能降低。在嗅觉系统中，抑制在信息处理中具有特别突出的作用，因为嗅球（OB）作为大脑中嗅觉信息的第一个中继站，含有异常大量的抑制性中间神经元。本综述总结了关于OB水平和初级嗅觉皮层中抑制性中间神经元的当前知识，以概述这些神经元如何影响嗅觉行为。我们还比较了健康衰老与作为最常见神经退行性疾病的AD之间不同嗅觉脑区中间神经元组成的变化。我们发现，嗅觉区域的病理生理变化反映了海马体和皮层区域的研究结果，这些结果表明AD中GABA能中间神经元有明显的细胞损失，但衰老过程中没有。通过所有嗅觉区域，不同中间神经元群体显示出的是易损性差异，而非脑区差异，其中生长抑素阳性细胞受影响最为严重。
