DOI: 10.1002/alz.078929 ISSN: 1552-5260

A systematic evaluation of hippocampal GABA levels in transgenic mouse models of amyloid and tau

André Nunes Mensch, Giovanna Carello‐Collar, Bruna Bellaver, Pamela C.L. Ferreira, Vanessa G. Ramos, Tharick A. Pascoal, Pedro Rosa‐Neto, Eduardo R Zimmer
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology

Abstract

Background

Alzheimer’s disease (AD) is characterized by the extracellular accumulation of amyloid‐β (Aβ) plaques and neuronal deposition of tau tangles, mainly in cortical regions and the hippocampus. Beyond these neuropathological hallmarks, it is suggested that neurotransmission dysfunctions, such as in the γ‐aminobutyric acid (GABA)ergic system, contribute to AD pathophysiology. However, the impact of Aβ and tau in the GABAergic system is still unknown. Thus, we aimed to examine GABA levels in the hippocampus of transgenic mouse models of Aβ and tau.

Method

We systematically reviewed the literature following the PRISMA 2020 guidelines. We searched PubMed and Web of Science databases for studies reporting GABA levels in the 3xTg‐AD and 5xFAD mouse models. These models present APP and PSEN1 mutations, but the 3xTg‐AD also harbors the MAPT P310L tau mutation, which is found in frontotemporal dementia.

Result

The search identified 3,576 articles. Six met the inclusion criteria (n = 26 3xTg‐AD and 26 wild‐type (WT); n = 16 5xFAD and 17 WT). The studies reported no significant differences in the levels of GABA in the hippocampus of 3xTg‐AD mice compared to their WT, but GABA levels decreased as a function of age. By contrast, the 5xFAD mouse model presented higher levels of GABA than their WT littermates.

Conclusion

Here, we show no significant changes in GABA levels in the hippocampus of 3xTg‐AD mice, whereas the levels of GABA were increased in the 5xFAD. Interestingly, the model harboring APP, PSEN1, and MAPT P310L mutations does not present changes in hippocampal levels of GABA. Our results suggest that Aβ alters GABA levels in the hippocampus, which may be an early change in AD. In addition, hippocampal GABAergic changes seem sensitive to different pathological features of AD.

More from our Archive