1H-MRS can monitor metabolites changes of lateral intraventricular BDNF infusion into a mouse model of Alzheimer's disease in vivo

Abstract

Proton magnetic resonance spectroscopy (1H-MRS) can provide noninvasive detection of brain metabolite changes in vivo in Alzheimer's disease (AD). AD is a prevalent neurodegenerative disorder characterized by deposition of β-amyloid peptides (Aβ) in multiple brain regions. Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor whose level has been shown to be decreased in AD. BDNF supplementation can offer improvement in AD. However, the means of evaluation are still relatively limited. In the present study, 1H-MRS was applied to evaluate the therapeutic effects of bilateral intraventricular BDNF infusion into APP+PS1 (amyloid precursor protein+presenilin 1) transgenic mice. For comparison to the 1H-MRS changes in the prefrontal cortex, Morris water maze (MWM) test, Fluoro-Jade B staining and immunofluorescence for Aβ, glial fibrillary acidic protein and tropomyosin-related kinase B (TrkB) were also performed. Our results showed that N-acetylaspartate (NAA) levels increased and myo-inositol levels decreased in Tg-BDNF mice compared with Tg-PBS mice. But NAA level in Tg-BDNF mice was still lower than that in wild-type mice at 6weeks after infusion. These changes correlated with increased immunoreactivity of TrkB, reduced compact Aβ peptide and FJB+ neurons in Tg-BDNF mice compared to Tg-PBS mice. However, Tg-BDNF mice did not present obvious changes in behavior in the MWM. Taken together, we suggest that 1H-MRS may be a sensitive means of evaluating metabolic changes in response to therapeutic strategies in AD. Moreover, BDNF, may be a viable means of offering trophic support during disease.