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Cerebellum neurotransmission during postnatal development: [Pt( O , O ′‐acac)(γ‐acac)(DMS)] vs cisplatin and neurotoxicity
Author(s) -
Piccolini Valeria Maria,
Esposito Alessandra,
Dal Bo Veronica,
Insolia Violetta,
Bottone Maria Grazia,
De Pascali Sandra Angelica,
Fanizzi Francesco Paolo,
Bernocchi Graziella
Publication year - 2015
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2014.10.006
Subject(s) - neurotoxicity , purkinje cell , neuroscience , medium spiny neuron , cerebellum , neurotransmitter , glutamate receptor , neurotransmission , cisplatin , pharmacology , biology , chemistry , toxicity , striatum , medicine , dopamine , central nervous system , chemotherapy , receptor
Several chemotherapeutic drugs are known to cause neurotoxicity. Platinum‐based agents in use or in clinical trials display neurotoxic potential accompanied by neurological complications; recent studies have identified a large number of behavioural issues in paediatric oncology patients. To understand the toxicity of platinum drugs at the molecular and cellular levels, this study compares the possible cytotoxic effects of an older platinum compound, cisplatin and a new platinum compound, [Pt( O , O ′‐acac)(γ‐acac)(DMS)], on the CNS of postnatally developing rats, which is much more vulnerable to injury than the CNS of adult rats. Since several drugs interact with neurotransmitters during neuronal maturation, we performed immunostainings with antibodies raised against markers of glutamate and GABA, the major neurotransmitters in the cerebellum. After a single injection of cisplatin at postnatal day 10 (PD10), the labelling of Purkinje cells with the neurotransmitter markers evidenced alterations between PD11 and PD30, i.e. atrophy of the dendrite tree, changes in the distribution of synaptic contacts of parallel and climbing fibres, delay in the elimination of transient synapses on cell soma and severely impaired pinceau formation at the axon hillock. After treatment with [Pt( O , O ′‐acac)(γ‐acac)(DMS)], the sole relevant change concerned the timing of climbing fibres elimination; the transient synapses disappearance on the Purkinje cell soma was delayed in some cells; instead, the growth of Purkinje cell dendrite tree was normal as was the formation of inhibitory synaptic contacts on these neurons. These findings add new evidence not only on the lower neurotoxicity of [Pt( O , O ′‐acac)(γ‐acac)(DMS)] vs cisplatin but also on the involvement of neurotransmitters and relative synaptic connections in the maturation of central nerve tissue.