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Prolonged impairment of astrocytic functions could increase the vulnerability of dopaminergic neurons in the substantia nigra (\n                      <jats:styled-content style=\"fixed-case\">SN<\/jats:styled-content>\n                      ), accelerate their degeneration and affect ability to compensate for partial degeneration at the presymptomatic stages of the disease. The aim of this study was to investigate the astrocyte depletion in the\n                      <jats:styled-content style=\"fixed-case\">SN<\/jats:styled-content>\n                      , its impact on the dopaminergic system functioning and multiple markers of energy metabolism during the early stages of neurodegeneration and compensation. We induced death of 30% of astrocytes by chronic infusion of fluorocitrate (\n                      <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>\n                      ) into the\n                      <jats:styled-content style=\"fixed-case\">SN<\/jats:styled-content>\n                      , simultaneously activating microglia response but sparing the dopaminergic neurons. The\n                      <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>\n                      effect was reversible after toxin withdrawal. Dopaminergic neurons were killed by 6\u2010hydroxydopamine causing transient locomotor disability, reversed with time showing compensatory potential. Death of astrocytes diminished the capability of the dopaminergic system to compensate for the degeneration of neurons and caused a local energy deprivation by decreasing lactate and glycogen amount. Studied markers suggest a shift in the usage of energy substrates, via increased glycogenolysis and glycolysis markers, ketone bodies availability and fatty acid transport in remaining cells. Peroxisome proliferator\u2010activated receptor\u2010gamma coactivator 1\u03b1 (PGC\u20101alpha) and AMP\u2010activated protein kinase (AMPK), the energy sensors, showed different regulation between the cell\u2010types. Increased neuronal expression of carnitine palmitoyltransferase 1c could play a role in the adaptation to metabolic stress in response to glia dysfunction. Astrocyte energetic support is one of the essential factors for neuronal compensatory mechanisms of dopaminergic system and might have a leading role in the presymptomatic Parkinson's disease stages.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Open science badges<\/jats:title>\n                    <jats:p>\n                      <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/jnc14605-gra-0001.png\" xlink:title=\"image\"\/>\n                    <\/jats:p>\n                    <jats:p>\n                      This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/cos.io\/our-services\/open-science-badges\/\">https:\/\/cos.io\/our-services\/open-science-badges\/<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14605-fig-0007-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  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