PURKINJE CELLS

  • “The effect of fluoride on murine thyroid function and cerebellar development was studied by administering NaF in drinking water (0.5 g/L) to pregnant and lactating mice, from the 15th day of pregnancy to the 14th day after delivery. Compared to a control group, the NaF-treated pups, at age 14 days, showed a 35% decrease in body weight, a 75% decrease in plasma free T4, and reductions in the cerebellar and cerebral protein concentrations by 27% and 17%, respectively. Consistent histological changes were present in the cerebellum of the treated mice with the external granular layer being markedly reduced or absent, the Purkinje cell bodies being poorly differentiated and arranged in a single layer at the surface of the internal granular layer, and with more apoptotic Purkinje cells being present.”
    [Trabels M,  Guermazi F, Zeghal N - Effect of fluoride on thyroid function and cerebellar development in mice” Fluoride 34(3): 165-173 (2001) Research Report 165]

   Total Purkinje cell counts have been shown to be significantly lower in the cerebellar hemisphere and vermis of autistic subjects (Ritvo et al, 1986).

   A most consistent finding is a reduction in granule and Purkinje cell density in the neocerebellum (Trottier et al, 1999).

   Purkinje cell gene expression is regulated by thyroid hormone (Koibuchi, 1998; Zou et al, 1994; Figueiredo et al, 1993). In hypothyroid rats, the expression of specific genes was retarded, indicating that the effect of thyroid hormone deficiency  may involve complex mechanisms such as impaired efficiency of axonal transport (Figueiredo et al, 1993)

   Hypothyroidism sharply reduces the rise in Purkinje cell mRNAs. T3 administration normalizes the process (Strait et al, 1992).

Gq/11:  Gq/11 are localized at postsynaptic extra-junctional membrane of cerebellar purkinje cells and hippocampal pyramidal cells (Tanaka et al, 2000).

See also: Reelin ; NGF

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Figueiredo BC, Almazan G, Ma Y, Tetzlaff W, Miller FD, Cuello AC - "Gene expression in the developing cerebellum during perinatal hypo- and hyperthyroidism" Brain Res Mol Brain Res 17(3-4):258-68 (1993) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=7685463&form=6&db=m&Dopt=r

Koibuchi N, Chin WW - "ROR alpha gene expression in the perinatal rat cerebellum: ontogeny and thyroid hormone regulation" Endocrinology 139(5):2335-41  (1998) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=9564842&form=6&db=m&Dopt=r

Ritvo ER, Freeman BJ, Scheibel AB, Duong T, Robinson H, Guthrie D, Ritvo A -"Lower Purkinje cell counts in the cerebella of four autistic subjects: initial findings of the UCLA-NSAC Autopsy Research Report" Am J Psychiatry 143(7):862-6  (1986) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=3717426&form=6&db=m&Dopt=r

Strait KA, Zou L, Oppenheimer JH - "Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development" Mol Endocrinol 6(11):1874-80(1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1282672&form=6&db=m&Dopt=r

Tanaka K, Shimatsu A, Imura H - "Iodothyronine 5-deiodinase in rat posterior pituitary" Biochem Biophys Res Commun 188(1):272-7  (1992) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=1417847&form=6&db=m&Dopt=r

Trottier G, Srivastava L Walker CD, - "Etiology of infantile autism: a review of recent advances in genetic and neurobiological research" J Psychiatry Neurosci 24(2):103-115 (1999)] FULL TEXT: http://www.cma.ca/jpn/vol-24/issue-2/0103.htm

Zhang Z, Xu X, Shen X, Xu X - "Effect of fluoride exposure on synaptic structure of brain areas related to learning-memory in mice" Wei Sheng Yan Jiu 28(4):210-2 (1999)
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=11938978&form=6&db=m&Dopt=r

  • "The learning-memory behavior was tested in mice on a Y-maze after drinking different concentration of sodium fluoride. The impairment on the structure of Gray 1 synaptic interface in the CA3 area of mice hippocampus were quantitatively analyzed by electron microscopy and computer image processing appliance. The main results are as follows: the learning ability of mice drinking high concentration of fluoride presented remarkable deterioration, the thickness of post-synaptic density (PSD) was decreased, and the width of synaptic cleft was remarkably increased. The results suggested that the impairment on the learning capability induced by fluorosis may be closely related with the pathological changes of synaptic structure in the brain of mice."

Zou L, Hagen SG, Strait KA, Oppenheimer JH - "Identification of thyroid hormone response element in rodent Pcp-2, a developmentally regulated gene of cerebellar Purkinje cells "J Biol Chem 9:13346-13352 (1994) http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=8175765&form=6&db=m&Dopt=r