Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    MDPI AG ; 2021
    In:  International Journal of Molecular Sciences Vol. 22, No. 17 ( 2021-08-31), p. 9466-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 22, No. 17 ( 2021-08-31), p. 9466-
    Abstract: (1) Background: Absence seizures (ASs) are sudden, transient lapses of consciousness associated with lack of voluntary movements and generalized 2.5–4 Hz spike-wave discharges (SWDs) in the EEG. In addition to the thalamocortical system, where these pathological oscillations are generated, multiple neuronal circuits have been involved in their modulation and associated comorbidities including the serotonergic system. Neuronal activity in one of the major synaptic input structures to the brainstem dorsal raphé nucleus (DRN), the lateral hypothalamus (LH), has not been characterized. (2) Methods: We used viral tract tracing and optogenetics combined with in vitro and in vivo electrophysiology to assess the involvement of the LH in absence epilepsy in a genetic rodent model. (3) Results: We found that a substantial fraction of LH neurons project to the DRN of which a minority is GABAergic. The LH to DRN projection can lead to monosynaptic iGluR mediated excitation in DRN 5-HT neurons. Neuronal activity in the LH is coupled to SWDs. (4) Conclusions: Our results indicate that a brain area involved in the regulation of autonomic functions and heavily innervating the RN is involved in ASs. The decreased activity of LH neurons during SWDs could lead to both a decreased excitation and disinhibition in the DRN. These results support a long-range subcortical regulation of serotonergic neuromodulation during ASs and further our understanding of the state-dependence of these seizures and some of their associated comorbidities.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2019364-6
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Acta Neuropathologica Communications, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2019-12)
    Type of Medium: Online Resource
    ISSN: 2051-5960
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2715589-4
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Molecular Oncology, Wiley, Vol. 14, No. 9 ( 2020-09), p. 2040-2057
    Abstract: Brain metastases are life‐threatening complications of triple‐negative breast cancer, melanoma, and a few other tumor types. Poor outcome of cerebral secondary tumors largely depends on the microenvironment formed by cells of the neurovascular unit, among which pericytes are the least characterized. By using in vivo and in vitro techniques and human samples, here we show that pericytes play crucial role in the development of metastatic brain tumors by directly influencing key steps of the development of the disease. Brain pericytes had a prompt chemoattractant effect on breast cancer cells and established direct contacts with them. By secreting high amounts of extracellular matrix proteins, pericytes enhanced adhesion of both melanoma and triple‐negative cancer cells, which might be particularly important in the exclusive perivascular growth of these tumor cells. In addition, pericytes secreted insulin‐like growth factor 2 (IGF2), which had a very significant pro‐proliferative effect on mammary carcinoma, but not on melanoma cells. By inhibiting IGF2 signaling using silencing or picropodophyllin (PPP), we could block the proliferation‐increasing effect of pericytes on breast cancer cells. Administration of PPP (a blood–brain barrier‐permeable substance) significantly decreased the size of brain tumors in mice inoculated with triple‐negative breast cancer cells. Taken together, our results indicate that brain pericytes have significant pro‐metastatic features, especially in breast cancer. Our study underlines the importance of targeting pericytes and the IGF axis as potential strategies in brain metastatic diseases.
    Type of Medium: Online Resource
    ISSN: 1574-7891 , 1878-0261
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2322586-5
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    Online Resource
    Online Resource
    Walter de Gruyter GmbH ; 2018
    In:  Bulletin of Medical Sciences Vol. 91, No. 1 ( 2018-07-01), p. 26-36
    In: Bulletin of Medical Sciences, Walter de Gruyter GmbH, Vol. 91, No. 1 ( 2018-07-01), p. 26-36
    Abstract: Proper functioning of the nervous system is largely dependent on the precise regulation of the neuronal environment. By shielding the central nervous system (CNS) from potentially harmful substances, the blood-brain barrier (BBB) has an indispensable role in this process. The BBB is a specialized system of endothelial cells lining brain microvessels, which – supported by pericytes and glial cells – form a selective barrier between the blood and the neural tissue. Under abnormal conditions, permeability of the BBB may increase, which may either trigger or aggravate the disease. Since CNS disorders – at least in their initial phase – usually do not involve the whole brain and spinal cord, but are localized to a certain region, our aim was to understand whether the BBB is regionally heterogeneous at the molecular level. By using bioinformatics tools, we analyzed expression levels of genes specific to cerebral endothelial cells, pericytes or astrocytes in different brain territories. Our results revealed regional heterogeneities in the expression of BBB-associated genes in both human and mouse. Expression pattern of efflux transporters – which have a major role in blocking passage of therapeutic agents through the BBB – proved to be diverse both among brain regions and between mouse and human. Our results indicate that: (1) in silico database analyses are suitable for group-based studies on gene functions, overcoming the limitations of single-gene analyses; (2) high-throughput tests should always be validated using other methods; (3) when using animal models, inter-species differences have to be always considered; (4) when comparing different brain regions, the BBB is heterogeneous at the molecular level, and this might have clinical significance.
    Type of Medium: Online Resource
    ISSN: 2537-5059
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2018
    detail.hit.zdb_id: 2977687-9
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages