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Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

Khalil OS, Pisar M, Forrest CM, Vincenten MC, Darlington LG, Stone TW - Eur. J. Neurosci. (2014)

Bottom Line: Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour.The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1.These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience and Psychology, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK.

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Effects of prenatal Ro61-8048 treatment on adult hippocampal CA1 dendritic spines. The photomicrographs show spines on an apical dendrite from a rat treated with vehicle (1) and a rat treated with Ro61-8048 (2). (A) Overall spine density. (B and C) Separately quantified densities of mushroom spines (B) and thin spines (C) in the CA1 apical dendrites. (D–F) Corresponding data for total spines (D), thin spines (E) and mushroom spines (F) on basal dendrites. Mushroom and thin spines were counted in successive 10-μm lengths of pyramidal neurons. *P < 0.05; **P < 0.01.
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fig02: Effects of prenatal Ro61-8048 treatment on adult hippocampal CA1 dendritic spines. The photomicrographs show spines on an apical dendrite from a rat treated with vehicle (1) and a rat treated with Ro61-8048 (2). (A) Overall spine density. (B and C) Separately quantified densities of mushroom spines (B) and thin spines (C) in the CA1 apical dendrites. (D–F) Corresponding data for total spines (D), thin spines (E) and mushroom spines (F) on basal dendrites. Mushroom and thin spines were counted in successive 10-μm lengths of pyramidal neurons. *P < 0.05; **P < 0.01.

Mentions: In the apical dendritic tree, the total spine density was no different in the Ro61-8048-exposed tissue (Fig.2A), although separate analysis of the thin and thick (mushroom-shaped) spines indicated a significant reduction in the number of the latter (two-tailed t-test, P = 0.007) (Fig.2B) with no significant difference in the population of thin spines (Fig.2C; two-tailed t-test, P = 0.54). The density of spines on the basal dendrites of CA1 neurons was significantly lower in tissue from rats exposed to Ro61-8048 in utero than in control tissue (two-tailed t-test, P = 0.036) (Fig.2D), but with no differential loss of thin spines (two-tailed t-test, P = 0.07) (Fig.2E) or thick mushroom spines (P = 0.75; Fig.2F).


Prenatal inhibition of the kynurenine pathway leads to structural changes in the hippocampus of adult rat offspring.

Khalil OS, Pisar M, Forrest CM, Vincenten MC, Darlington LG, Stone TW - Eur. J. Neurosci. (2014)

Effects of prenatal Ro61-8048 treatment on adult hippocampal CA1 dendritic spines. The photomicrographs show spines on an apical dendrite from a rat treated with vehicle (1) and a rat treated with Ro61-8048 (2). (A) Overall spine density. (B and C) Separately quantified densities of mushroom spines (B) and thin spines (C) in the CA1 apical dendrites. (D–F) Corresponding data for total spines (D), thin spines (E) and mushroom spines (F) on basal dendrites. Mushroom and thin spines were counted in successive 10-μm lengths of pyramidal neurons. *P < 0.05; **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368408&req=5

fig02: Effects of prenatal Ro61-8048 treatment on adult hippocampal CA1 dendritic spines. The photomicrographs show spines on an apical dendrite from a rat treated with vehicle (1) and a rat treated with Ro61-8048 (2). (A) Overall spine density. (B and C) Separately quantified densities of mushroom spines (B) and thin spines (C) in the CA1 apical dendrites. (D–F) Corresponding data for total spines (D), thin spines (E) and mushroom spines (F) on basal dendrites. Mushroom and thin spines were counted in successive 10-μm lengths of pyramidal neurons. *P < 0.05; **P < 0.01.
Mentions: In the apical dendritic tree, the total spine density was no different in the Ro61-8048-exposed tissue (Fig.2A), although separate analysis of the thin and thick (mushroom-shaped) spines indicated a significant reduction in the number of the latter (two-tailed t-test, P = 0.007) (Fig.2B) with no significant difference in the population of thin spines (Fig.2C; two-tailed t-test, P = 0.54). The density of spines on the basal dendrites of CA1 neurons was significantly lower in tissue from rats exposed to Ro61-8048 in utero than in control tissue (two-tailed t-test, P = 0.036) (Fig.2D), but with no differential loss of thin spines (two-tailed t-test, P = 0.07) (Fig.2E) or thick mushroom spines (P = 0.75; Fig.2F).

Bottom Line: Golgi-Cox silver staining revealed decreased overall numbers and lengths of CA1 basal dendrites and secondary basal dendrites, together with fewer basal dendritic spines and less overall dendritic complexity in the basal arbour.The number of neuron terminals staining for vesicular glutamate transporter (VGLUT)-1 and VGLUT-2 was increased by Ro61-8048, with no change in expression of vesicular GABA transporter or its co-localisation with vesicle-associated membrane protein-1.These data support the view that constitutive kynurenine metabolism normally plays a role in early embryonic brain development, and that interfering with it has profound consequences for neuronal structure and morphology, lasting into adulthood.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience and Psychology, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK.

Show MeSH