Lactation is a temporary but complex physiological condition in which hormones and neurogenic stimulation from suckling cause maternal brain plasticity. It has been shown that lactation prevents cell damage induced by excitotoxicity in the dorsal hippocampus of the dam after peripheral administration of kainic acid (KA). The aim of this study was to determine whether lactation protects the maternal hippocampus against damage induced by intracerebral application (ICV) of KA and if lactation decreases, or only delays, this damaging effect of KA. Cell damage was assessed by Fluoro-Jade C staining in the hippocampus of virgin and lactating rats 24 or 72 h after ICV KA. Lactation prevented cell damage of the pyramidal layers of the hippocampus (CA1, CA3, and CA4), as compared to virgin rats. The longer period of KA exposure increased the difference in cell damage between these two conditions. The present results confirm that lactation is a natural model for neuroprotection, since it effectively prevents acute and chronic cell damage of the hippocampus induced by exposure to KA.
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http://dx.doi.org/10.1016/j.neulet.2009.06.017 | DOI Listing |
Biomacromolecules
January 2025
School of Life Science, South China Normal University, Guangzhou 510631, China.
Cerebral ischemic stroke, neuronal death, and inflammation bring difficulties in neuroprotection and rehabilitation. In this study, we developed and designed the ability of natural lactoferrin-polyethylene glycol-polyphenylalanine-baicalein nanomicelles (LF-PEG-PPhe-Bai) to target and reduce these pathological processes, such as neurological damage and cognitive impairment in the stages of poststroke. Nanomicelles made from biocompatible materials have improved bioavailability and targeted distribution to afflicted brain areas.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom.
Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Center for Medical Research and Innovation, Shanghai Pudong Hospital, Institutes of Biomedical Sciences, Chinese Academy of Medical Sciences (RU069), Medical College of Fudan University, Shanghai 201399, China.
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Pediatric Surgical Research Laboratories, Massachusetts General Hospital, Boston, MA 02114.
Anti-Müllerian hormone (AMH) protects the ovarian reserve from chemotherapy, and this effect is most pronounced with Doxorubicin (DOX). However, DOX toxicity and AMH rescue mechanisms in the ovary have remained unclear. Herein, we characterize the consequences of these treatments in ovarian cell types using scRNAseq.
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