Histaminergic modulation of striatal development
<p>Inadequate synthesis of the neurotransmitter histamine in the brain has been suggested to be one of causes of Tourette’s syndrome and several psychiatric diseases. Previous findings suggested that dysfunction of the corticostriatal circuits are associated with such mental disorders. Indeed,...
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| Format: | Thesis |
| Language: | English |
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2020
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| _version_ | 1797070230154903552 |
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| author | Han, S |
| author2 | Ellender, T |
| author_facet | Ellender, T Han, S |
| author_sort | Han, S |
| collection | OXFORD |
| description | <p>Inadequate synthesis of the neurotransmitter histamine in the brain has been suggested to be one of causes of Tourette’s syndrome and several psychiatric diseases. Previous findings suggested that dysfunction of the corticostriatal circuits are associated with such mental disorders. Indeed, recent research has reported a hypofunction of histamine in patients with Tourette’s syndrome and obsessive-compulsive disorder in human and animal studies. However, the functional role of histamine in young developing animal brains is poorly known. Firstly, this study investigated whether and to what extent histamine plays a significant role in the corticostriatal circuit in the developing mouse brain. Secondly, the study investigated whether and to what extent histamine affects neurogenesis in the striatum in the embryonic mouse brain. Towards the first aim, the study recruited three postnatal young age period mice (postnatal (P)3-6 days, P9-12 days and P21+ days) and applied extracelluar field recordings of the corticostriatal transmission. As a result, the study found that histamine negatively modulates the corticostriatal synaptic transmission in all of young age period mice, acting at the H3 receptors. In addition, histamine facilitated long-term potentiation of the corticostriatal synapses in the P9-12 period, but blocked it in the P21+ period, whereas the baseline condition showed long-term facilitation in the P21+, not the P9-12 periods. Collective analysis of this long-term plasticity experiment revealed that the dorsolateral striatum (DLS) is more likely to be facilitated than the dorsomedial striatum (DMS). Histamine’s negative modulation on the corticostriatal synaptic transmission is found in developing age periods, which was found in only adult mice brains in past studies. Also histamine’s opposite effect on the corticostriatal long-term plasticity in the P9-12 and P21+ periods implies that histamine may cause significant change in the dynamics of synaptic properties in particular developing age periods. For the second aim, the study injected α-fluoromethylhistidine (α-FMH) into the ventricle of embryonic mouse brain at embryonic day (E)12.5 and E15.5. The study then collected their brains 2-3 days after the application of α-FMH to compare the size of the striatum and proliferative zones between control and α-FMH conditions. Finally, a reduced size of striatum was observed in E15.5 brains (medial section) treated with α-FMH than those in control conditions. However, the study could not make further conclusions due to the small number of samples.</p> |
| first_indexed | 2024-03-06T22:35:56Z |
| format | Thesis |
| id | oxford-uuid:59e461ac-fbdd-4ef4-92c8-c772f2f70980 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:35:56Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | oxford-uuid:59e461ac-fbdd-4ef4-92c8-c772f2f709802022-03-26T17:12:31ZHistaminergic modulation of striatal developmentThesishttp://purl.org/coar/resource_type/c_bdccuuid:59e461ac-fbdd-4ef4-92c8-c772f2f70980neurosciencepharmacologypsychiatryEnglishHyrax Deposit2020Han, SEllender, TSharp, T<p>Inadequate synthesis of the neurotransmitter histamine in the brain has been suggested to be one of causes of Tourette’s syndrome and several psychiatric diseases. Previous findings suggested that dysfunction of the corticostriatal circuits are associated with such mental disorders. Indeed, recent research has reported a hypofunction of histamine in patients with Tourette’s syndrome and obsessive-compulsive disorder in human and animal studies. However, the functional role of histamine in young developing animal brains is poorly known. Firstly, this study investigated whether and to what extent histamine plays a significant role in the corticostriatal circuit in the developing mouse brain. Secondly, the study investigated whether and to what extent histamine affects neurogenesis in the striatum in the embryonic mouse brain. Towards the first aim, the study recruited three postnatal young age period mice (postnatal (P)3-6 days, P9-12 days and P21+ days) and applied extracelluar field recordings of the corticostriatal transmission. As a result, the study found that histamine negatively modulates the corticostriatal synaptic transmission in all of young age period mice, acting at the H3 receptors. In addition, histamine facilitated long-term potentiation of the corticostriatal synapses in the P9-12 period, but blocked it in the P21+ period, whereas the baseline condition showed long-term facilitation in the P21+, not the P9-12 periods. Collective analysis of this long-term plasticity experiment revealed that the dorsolateral striatum (DLS) is more likely to be facilitated than the dorsomedial striatum (DMS). Histamine’s negative modulation on the corticostriatal synaptic transmission is found in developing age periods, which was found in only adult mice brains in past studies. Also histamine’s opposite effect on the corticostriatal long-term plasticity in the P9-12 and P21+ periods implies that histamine may cause significant change in the dynamics of synaptic properties in particular developing age periods. For the second aim, the study injected α-fluoromethylhistidine (α-FMH) into the ventricle of embryonic mouse brain at embryonic day (E)12.5 and E15.5. The study then collected their brains 2-3 days after the application of α-FMH to compare the size of the striatum and proliferative zones between control and α-FMH conditions. Finally, a reduced size of striatum was observed in E15.5 brains (medial section) treated with α-FMH than those in control conditions. However, the study could not make further conclusions due to the small number of samples.</p> |
| spellingShingle | neuroscience pharmacology psychiatry Han, S Histaminergic modulation of striatal development |
| title | Histaminergic modulation of striatal development |
| title_full | Histaminergic modulation of striatal development |
| title_fullStr | Histaminergic modulation of striatal development |
| title_full_unstemmed | Histaminergic modulation of striatal development |
| title_short | Histaminergic modulation of striatal development |
| title_sort | histaminergic modulation of striatal development |
| topic | neuroscience pharmacology psychiatry |
| work_keys_str_mv | AT hans histaminergicmodulationofstriataldevelopment |