RGD Reference Report - Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus. - Rat Genome Database

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Diabetes alters KIF1A and KIF5B motor proteins in the hippocampus.

Authors: Baptista, FI  Pinto, MJ  Elvas, F  Almeida, RD  Ambrosio, AF 
Citation: Baptista FI, etal., PLoS One. 2013 Jun 12;8(6):e65515. doi: 10.1371/journal.pone.0065515. Print 2013.
RGD ID: 11059542
Pubmed: PMID:23776493   (View Abstract at PubMed)
PMCID: PMC3680435   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0065515   (Journal Full-text)

Diabetes mellitus is the most common metabolic disorder in humans. Diabetic encephalopathy is characterized by cognitive and memory impairments, which have been associated with changes in the hippocampus, but the mechanisms underlying those impairments triggered by diabetes, are far from being elucidated. The disruption of axonal transport is associated with several neurodegenerative diseases and might also play a role in diabetes-associated disorders affecting nervous system. We investigated the effect of diabetes (2 and 8 weeks duration) on KIF1A, KIF5B and dynein motor proteins, which are important for axonal transport, in the hippocampus. The mRNA expression of motor proteins was assessed by qRT-PCR, and also their protein levels by immunohistochemistry in hippocampal slices and immunoblotting in total extracts of hippocampus from streptozotocin-induced diabetic and age-matched control animals. Diabetes increased the expression and immunoreactivity of KIF1A and KIF5B in the hippocampus, but no alterations in dynein were detected. Since hyperglycemia is considered a major player in diabetic complications, the effect of a prolonged exposure to high glucose on motor proteins, mitochondria and synaptic proteins in hippocampal neurons was also studied, giving particular attention to changes in axons. Hippocampal cell cultures were exposed to high glucose (50 mM) or mannitol (osmotic control; 25 mM plus 25 mM glucose) for 7 days. In hippocampal cultures incubated with high glucose no changes were detected in the fluorescence intensity or number of accumulations related with mitochondria in the axons of hippocampal neurons. Nevertheless, high glucose increased the number of fluorescent accumulations of KIF1A and synaptotagmin-1 and decreased KIF5B, SNAP-25 and synaptophysin immunoreactivity specifically in axons of hippocampal neurons. These changes suggest that anterograde axonal transport mediated by these kinesins may be impaired in hippocampal neurons, which may lead to changes in synaptic proteins, thus contributing to changes in hippocampal neurotransmission and to cognitive and memory impairments.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOKif1a (Rattus norvegicus)11059542; 11059542mRNA:increased expression:hippocampusRGD 
Experimental Diabetes Mellitus  ISOKif5b (Rattus norvegicus)11059542; 11059542mRNA:increased expression:hippocampusRGD 
Experimental Diabetes Mellitus  IEP 11059542; 11059542mRNA:increased expression:hippocampusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon  IDA 11059542 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kif1a  (kinesin family member 1A)
Kif5b  (kinesin family member 5B)

Genes (Mus musculus)
Kif1a  (kinesin family member 1A)
Kif5b  (kinesin family member 5B)

Genes (Homo sapiens)
KIF1A  (kinesin family member 1A)
KIF5B  (kinesin family member 5B)

Objects referenced in this article
Gene KIF5A kinesin family member 5A Homo sapiens
Gene Kif5a kinesin family member 5A Mus musculus
Gene Kif5a kinesin family member 5A Rattus norvegicus

Additional Information