Cerebral energy metabolism in Alzheimer disease (AD) has recently been given increasing attention. This study focuses on the alterations of cerebral lactate metabolism in the double-transgenic amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD. Immunofluorescence staining and Western blotting analysis were used to identify the alterations of lactate content and lactate transporters (MCT1, MCT2, MCT4) in APP/PS1 mouse brains, which display amyloid beta plaques, reduced amounts of neurons and oligodendrocytes, and increased quantity of astrocytes. We found that lactate content and expressions of cerebral MCT1, MCT2, and MCT4 were decreased in APP/PS1 mice. In particular, lactate dehydrogenase A (LDHA) and B (LDHB) were reduced in neurons with increased ratios of LDHA and LDHB. This study suggests that the decreases of cerebral lactate content and lactate transporters may lead to the blockage of lactate transport from glia to neurons, resulting in neuronal lactate deficit. The increased ratio of neuronal LDHA and LDHB may represent a reaction of neurons to lactate deficit, although it cannot reverse the energy deficiency in neurons.

Demyelinating diseases, such as multiple sclerosis (MS), are kinds of common diseases in the central nervous system (CNS), and originated from myelin loss and axonal damage. Oligodendrocyte dysfunction is the direct reason of demyelinating lesions in the CNS. Nitric oxide (NO) plays an important role in the pathological process of demyelinating diseases. Although the neurotoxicity of NO is more likely mediated by peroxynitrite rather than NO itself, NO can impair oligodendrocyte energy metabolism through mediating the damaging of mitochondrial DNA, mitochondrial membrane and mitochondrial respiratory chain complexes. In the progression of MS, NO can mainly mediate demyelination, axonal degeneration and cell death. Hence, in this review, we extensively discuss endangerments of NO in oligodendrocytes (OLs), which is suggested to be the main mediator in demyelinating diseases, e.g. MS. We hypothesize that NO takes part in MS through impairing the function of monocarboxylate transporter 1, especially causing axonal degeneration. Then, it further provides a new insight that NO for OLs may be a reliable therapeutic target to ameliorate the course of demyelinating diseases.